14- After leaving the inn, Ezio met with Machiavelli and discussed his plan to rid Rome of the menace known as Cesare Borgia and his allies that gave him power. As the two were talking, a thief attempted to steal money from Ezio, but Ezio easily overpowered him and took back his money. Ezio returned to Machiavelli and talked about his plans further, as they made their way to a contact whose job was to intercept a letter, though they found that he had been caught. Machiavelli and Ezio assisted the thief in defeating his attackers, before Ezio chased after and swiped the letter from the original courier.
Ezio began making his way back to Machiavelli, but he was attacked by a sect of wolf-men. Repelling the attackers, Ezio proceeded to investigate where they came from. After emerging from the underground, Ezio departed to find Machiavelli once more.
15- Letting his horse return to the stables, Ezio bypassed the city guards using the tunnels founded by his father. They led him to the Tiber Island headquarters where he met with Fabio Orsini, the cousin of Bartolomeo d'Alviano. From the headquarters, Ezio took leave to help and recruit the thieves, mercenaries and courtesans to the Assassins' cause.
16- Ezio arrived at the La Volpe Addormentata and requested aid from La Volpe, a thief and fellow Assassin. Believing Machiavelli of betraying the Order, La Volpe turned Ezio down hastily. In an attempt to prove his treachery, La Volpe led him to a meeting between Machiavelli and a city guard. Once Machiavelli had left, a fight broke out between thieves and several Borgia guards. La Volpe requested Ezio's help in keeping one of the thieves' son, Claudio, from being killed, and so Ezio dispatched many of the Borgia guards to save him.
Subsequently, Ezio escorted the young thief and directed him back to La Volpe and his father. After the rescue, Ezio returned to La Volpe Addormentata and enlisted La Volpe's aid, though the thief mentioned that he was still suspicious of Machiavelli. After this, the Thieves Guild was renovated into an inn, and Ezio assigned the thieves with the task of locating the Apple of Eden.
17- Arriving at the Barracks where Bartolomeo was stationed, Ezio was greeted kindly by his old friend and introduced to Bartolomeo's wife, Pantasilea Baglioni. However, Bartolomeo was alerted to an attack by Borgia guards, and rushed to the battle to protect his fortification.
18- Accompanying Bartolomeo, Ezio and the mercenaries fought back the attacking soldiers and sent them fleeing. Following the battle, the Barracks were revamped and Ezio explained to Bartolomeo the forces he needed. He assigned Bartolomeo and his mercenaries to keep an eye on Cesare's men, making sure to notify the Assassin if anything surfaced. Afterwards, Bartolomeo left for the fighting ring downstairs, claiming that he had bet money on the next match as Ezio took his leave.
19- After his arrival at the Rosa in Fiore, Ezio attempted to locate the owner of the place, Madonna Solari, but soon found out that she had been taken hostage by slave traders. Ezio left the brothel and began searching for the boat where she was being held. Once there, he gave the slave traders the thousand ducats ransom, in exchange for Madonna Solari's life. However, without hesitation, the slave traders slit Solari's throat. Forced into action, Ezio killed all the bandits present on the boat, before whispering one last word in the head slave trader's ear and leaving.
20- Ezio returned to the Rose in Fiore and discovered that his mother and sister never left for Florence, but traveled to Rome instead. Without a leader, the courtesans were in distress, but Claudia offered to take the position. After adopting the role as the brothel's Madame, the Rosa in Fiore was renovated and Ezio tasked Claudia's girls with locating Caterina Sforza.
21- Following the renovation, Ezio questioned Claudia on the location of Caterina, who claimed that her girls were working on it. Afterwards, Claudia attempted to make amends, but she stopped before she could say anything. Ezio, after he finished the conversation, left the brothel.
22- Reuniting with Machiavelli and the others at the Tiber Island hideout, Ezio discovered the location of Caterina Sforza from Claudia. With this information, he claimed he would infiltrate the Castel Sant'Angelo, not only to rescue Caterina, but also to take the lives of Rodrigo and Cesare Borgia.
23- On arriving at the Castel, Ezio witnessed Cesare's sister, Lucrezia Borgia, step out of a carriage with a prisoner, who turned out to be Caterina. On seeing this, Ezio tried to convince Machiavelli to let him rescue her, claiming that they were going to torture her; Machiavelli replied that Rodrigo and Cesare's deaths were the top priority. Scaling the walls of the Castel, Ezio eventually located Cesare and witnessed as he greeted Lucrezia, before eavesdropping on their conversation. Cesare soon left, leaving Ezio to wonder where he was departing to and for what reason.
24- Lucrezia entered the cell in which Caterina was being held and roughly beat her, which Ezio oversaw through the window. Once Lucrezia had left, taking the key along with her, the Assassin soon made his way inside the Castel, and upon locating Caterina, Ezio made plans to rescue her.
25- Ezio discovered Lucrezia flirting with her lover, Pietro Rossi. Once he had left, Ezio confronted Lucrezia and took out the guards who tried to stop him. Restraining her, Ezio carried Lucrezia to Caterina's cell, and once there, the Assassin freed Caterina and put Lucrezia in her cell, before the Borgia woman was knocked out on the cell's bars. Leaving the Castel, an explosion was heard, distracting the guards and giving both Ezio and Caterina the time to escape.
26- Ezio returned to Machiavelli and informed him that Cesare and Rodrigo left before he could strike, though La Volpe was not convinced that it was a coincidence. Caterina had arrived and was being tended to by a doctor, as Ezio was made the Mentor of the Italian Assassins, though he was told to keep it a secret so that a "formal" vote could happen. From there, Ezio talked to Machiavelli about his plan to rebuild the Brotherhood back to its former glory.
27- Ezio began recruiting many of Rome's oppressed citizens for his cause by assisting their struggle against the Borgia. He soon began hearing a strange voice that was calling him, and discovered that it was his old friend, Leonardo da Vinci. Leonardo claimed that he was one step ahead of them and once had possession of the Apple, though it had been taken from him by Rodrigo. He then explained to Ezio about some of the contraptions he was obligated to make for the Borgia, stating that they consisted of the Tank, among others. During their encounter, Ezio requested Leonardo to remake his Codex weapons. Leonardo agreed, but required payment for the materials. After Ezio had funded the inventor, Leonardo left, explaining to Ezio that he was planning to "go shopping for supplies."
28- Soon after he returned to the Hideout, Ezio planned his assassination of Octavian de Valois. Accompanying this, Machiavelli told Caterina of the danger she was in, and explained to her that she must leave the city, though her children were already safe in Florence. As a result, Caterina made her preparations to leave.
29- Confronting Caterina, Ezio argued with her about the night they spent at the Villa, claiming that she used him, and admitted that he did not rescue her because of the cause, with the room falling to silence. Soon enough, Caterina left, leaving Ezio in wonder.
30- Locating a senator who went by the name of Egidio Troche, Ezio managed to dispatch several guards who were harassing the senator for money. Traversing through the streets to evade the guards, Ezio escorted Egidio to his home, and from there, they discussed Cesare's banker, Juan Borgia. Offering to pay the senator's debts to Juan, Ezio gave the man the money he needed and waited for the time when Egidio would be forced to give the money to the Borgia.
31- Ezio tailed Egidio, and soon watched as the senator passed the money over to the Banker's guards. From there, the guards escorted Egidio to the Pantheon, where they came across a Borgia captain named Luigi Torcelli. Egidio handed over the money to the captain, who entered the building to count it. Ezio swiftly scaled the Pantheon's walls and infiltrated it from above, giving him enough time to kill Luigi, take his armor and disguise himself in his place. Afterwards, on managing to call off the guards from killing Egidio, Ezio navigated around Rome and managed to gain entrance to the Banker's party.
32- Luigi's body was soon found and the guards were on the lookout for Ezio, though he managed to blend and move through the crowd, following the money until it changed hands to the Banker himself. While he left the money where Claudia's courtesans were able steal it, Ezio followed the Banker into the celebration. There, Cesare made a speech before leaving the area, as Ezio watched the Banker flirt with a courtesan.
33- The night went on, and soon Ezio was discovered, but he managed to perform the final kill on the Banker and exchange words before he passed. Once back at the Rosa in Fiore, Ezio found the same woman who the Banker had been with, injured. It turned out that the Banker molested her and left her for dead, but she was saved by possible recruits. Claudia then forced Ezio out so her girls could get everything sorted.
34- Ezio refreshed himself at the Hideout and quickly made haste for the Rosa in Fiore, to which he saw the sign of a struggle, though he was greeted by the same girl who had been molested by Juan Borgia. Ezio had a short discussion with Claudia once he knew his mother and she were safe, and he was paid interest on his investment of renovating the brothel before he left.
35- Leonardo was at La Volpe Addormentata, which Ezio soon found out when he was pulled into a dark room. From there, Leonardo briefly talked with Ezio, saying that his friend Salaì knew he was here, but wouldn't betray his trust. They exchanged in pleasantries, and Ezio was soon given back his Codex weapons that he lost, as well as a new item named poison darts. With this, Ezio then saw La Volpe and told him of his intentions to track Pietro, Lucrezia's lover. The two learned from thieves about the location of Micheletto Corella, an associate of Cesare, to which La Volpe then expressed to Ezio about how he believed Machiavelli was a traitor, and told him to do something about it before he did. Ezio then gathered a horse from La Volpe and visited his sister, and was given backup Codex weapons, before he decided to put his apprentices to good use.
36- Ezio overlooked on a meeting involving Cesare himself, Micheletto and Francesco Troche, where they discussed about Egidio's actions of warning the Venetians about Cesare's war plans. While Francesco pleaded for forgiveness, Cesare no longer wanted to hear excuses, and ordered Micheletto to strangle him, before the Templar requested his guards to dump Francesco's body in the Tiber. After Cesare departed, Ezio followed Micheletto once he had found out that Pietro was in a passion play at the Colosseum. With this, Ezio infiltrated it and ordered his recruits to put on the armor that he had stolen from the men who were meant to be in the play. Soon enough, as the play progressed, Ezio attempted to assassinate Micheletto, though in the end, he spared him and saved Pietro. After Ezio carried Lucrezia's lover to a doctor, as he had drank poisoned wine, the Assassin received a key to the Castel Sant'Angelo from Pietro. After this, Ezio came across a thief who was present at the Villa attack, but as he tried to talk to him, the thief sprinted away. Confused, Ezio chased after the man and tackled him to the ground, though to his surprise, Ezio learned that the thief was, in fact, the traitor, and not Machiavelli who La Volpe suspected.
37- Attempting to find La Volpe, Ezio was urgently requested by his mother to hunt down some traitors of the courtesans, though Ezio quickly left to find Machiavelli once more.
38- Ezio rode towards La Volpe Addormentata and found La Volpe with his dagger, ready to take Machiavelli's life. However, he was stopped as Ezio cut him off and revealed the letter to La Volpe, as well as the betrayal of one of his own men. To this, Machiavelli was relieved and claimed he would substitute the letter to keep them off track, and La Volpe then told Ezio of a new bunch of thieves in the city, known as the Cento Occhi. In response, however, Ezio explained that they would not be a problem.
39- Making his way to the barracks, Ezio immediately sensed that something was wrong and rushed to meet his friend. Once there, he discovered that the French had once again put pressure on Bartolomeo's men, and after an assault on the Barracks, Ezio managed to close all the entrances and keep the French soldiers out. Subsequently, the Baron de Valois approached the Barracks, though he kept a safe distance, and revealed to Bartolomeo that he had kidnapped his wife Pantasilea. He claimed that if Bartolomeo wanted her back alive, he would have to surrender by dawn, and in a desperate attempt to rescue her, Bartolomeo charged out once, followed by Ezio and a group of mercenaries.
40- Ezio formed a plan and put it into action after he managed to steal 20 Frenchman armor to disguise Bartolomeo's mercenaries. They marched down to where the Baron was stationed and brought the Captain General to him. Ezio used his gun as a distraction but the Baron fled. Ezio followed him but was forced to sneak around or else the Baron would have killed Pantasilea. Ezio quietly navigated around and once within range Ezio struck, killing Valois. Bartolomeo entered and comforted his wife, before they walked off and Pantasilea quietly thanked Ezio.
41- Ezio was finally made official Mentor of the Assassin Brotherhood and his sister, Claudia, was inducted into the Assassin Order. They went to the rooftop of their hideout and Claudia performed her first Leap of Faith. Machiavelli then claimed he would write a book about Ezio one day but Ezio responded that if he did, he should make it short and then leapt from the rooftop.
42- Ezio infiltrated the Castel and overheard Lucrezia being told by a servant that Cesare was back from his journey. Lucrezia then left to ponder why Rodrigo hadn't told her.
43- Ezio managed to locate a window through which he could oversee Cesare arguing with Rodrigo. Cesare was in denial, believing that his father had the Baron and the Banker killed. Rodrigo admitted that the Assassins were responsible. Cesare then bit an apple, as Lucrezia rushed in to say that it was poisoned. Cesare then spat it out and killed Rodrigo with it. Lucrezia acknowledged that she had known Rodrigo had taken the Apple and Cesare revealed that he never loved Lucrezia and started choking her, demanding the Apple. Eventually she gave in and Cesare tried to escape as Ezio climbed in through the window. From there, he closed the eyes of the dead Pope and was told the location of the Apple; with this information, Ezio took his leave.
44- Escaping the Castel, Ezio made it to the Apple's location before Cesare despite Cesare being more likely to have ridden by horse. Ezio used the power of the Apple to aid in his escape from the basilica before blending in with the crowd, wondering how long until news of Rodrigo Borgia's death would spread and when a new Pope would take his place.
45- Ezio returned to the hideout and informed Machiavelli that although Rodrigo was dead, Cesare still lived. Machiavelli explained to Ezio that without Rodrigo to hold him back, Cesare could still gain back what the Assassins had taken from him. Ezio then went to confront Cesare who was trying to regain his title. Ezio intercepted and killed those who Cesare had tried to persuade, however he escaped before Ezio could take his life.
46- Ezio tracked Cesare to the Colosseum and found him trying to use the next Pope who had been elected. Ezio's arrival scared off the Cardinals who Cesare was trying to convince to change the Pope they'd selected for the position. Cesare's guards then surrounded Ezio and tried to fight him but they all fell; during the battle itself Ezio was truly injured and Cesare once again escaped.
47- Finding Cesare at the very gates that led into Rome, Ezio saw many of Cesare's followers group there, mostly guards. Ezio and the other Assassins gathered at the gate and attempted to fight back the Borgia guards. Towards the end of the battle, Cesare believed that Micheletto's army had massed behind him but instead, under the instruction of Fabio Orsini, they arrested Cesare instead of aiding him as he had thought. Screaming that no chains or man could defeat him or hold him, Cesare was dragged off to prison.
48- Ezio was reunited with Leonardo once more although was not convinced Cesare would be held by chains. Ezio embarked on a journey with Claudio, the young thief he had once rescued, to locate Cesare once he broke out of prison and soon, hijacked Cesare's ship and made his way back to Ostia.
49- Ezio discussed Cesare's fate with his ally, the new Pope, Julius II. Not expecting resources to be provided to him, he was told to locate somebody who was close to Micheletto and who might know something of their whereabouts.
50- Pondering why the Apple would not show Ezio where Cesare was, Ezio called a meeting of the Brotherhood where Machiavelli stated that a victory is not a victory unless absolute and then explained that Cesare is, in fact, alive and so is his former henchman, Micheletto. Ezio and Machiavelli journey to find Micheletto but soon, Claudia is kidnapped and held hostage. She is soon saved by Ezio who shows no mercy at first but in the end, ends the suffering of the kidnapper. They now know for sure that Micheletto is alive.
51- Ezio tracked Micheletto down and imprisoned hims in the same place Ezio's father spent his last days, a cell inside the Palazzo della Signoria. Inside, Micheletto was tortured and interrogated, and his days as a killer were done. Ezio, however, would not be so sure that they could break Micheletto considering he was very strong willed.
52- Ezio discovered that Pope Julius knew of the Apple, as the Pope himself asks about its power. Ezio immediately knew who told the Pope, Leonardo's friend Salaì. Ezio explained its powers and what the Borgia intended to do with it which the Pope understood.
53- Ezio located Cesare's old physician, Gaspar Torella and gained some idea of where Cesare might be. Spain was the first thing Gaspar would guess, considering Cesare's Spanish heritage.
54- Ezio found out from Machiavelli that Micheletto has escaped and realised that they must track him with the Apple before it's too late.
55- Ezio uses the Apple to locate Micheletto who appears to be in Navarre, then through the Apple, Ezio sees a final picture of a massive, wealthy seaport, with ships drawn up on a sea and an army which was gathering. Ezio, however, had no clue what any of these places meant.
56- Rosa, a woman whom Ezio had met in Venice, takes control of the Rosa in Fiore and is left in charge along with La Volpe to watch over Rome while Ezio and Machiavelli leave to hunt down Micheletto.
57- Ezio brought the Apple to Leonardo and tried to activate it, from there Ezio heard a noise which Machiavelli and Leonardo cannot seem to hear. It seemed to be the Apple communicating with him, instructing him to take the Apple to a Vault under Capitoline Hill and leave it there. Afterwards, it tells him to travel to Naples where Micheletto was trying to reach Valencia. Ezio then explained to his friends that the next destination is Naples. They arrive in Naples on Ezio's 46th birthday, where they learn much of Micheletto's destination from a lady who appeared to know much about him and soon enough they go further to hunt down Micheletto on ship.
58- One of three survivors who had not killed is found by Ezio who finishes the job, showing no mercy, but as he was dying the man spoke of Micheletto who was rushing to Castillo de la Mota where Cesare was being held. From there, Ezio left and continued on with the hunt.
59- Praying that they were in time to thwart Micheletto's plan, they retrieved their belongings from the Lone Wolf Inn and set off.
60- Micheletto made it to the Castillo and freed his former master, Cesare Borgia, who was already contemplating the slowest death possible to the Assassin.
61- Delayed because Leonardo was ill, Ezio discovered that Cesare escaped and wished to leave Leonardo but Machiavelli restrained. Events were to prove him right and Leonardo invaluable.
62- Killed by Cesare, Micheletto's body is discovered and now knowing where to go, Ezio and his two companions go their separate ways.
63- Ezio travelled across Spain and arrived at his destination, finding it under siege. While there, he needed to restock on weapons which he was kindly provided by a man who had what he needed.
64- Riding his horse through the battle, Ezio eventually loses his steed in the conflict. Ezio still traversed on and witnessed a harsh action by Cesare in which he ordered his guards to slit a woman's throat just for showing consideration and concern for her son.
65- Ezio soon found Cesare on the castle walls in which Ezio scaled before the two engaged in a heated battle. Ezio eventually overpowered Cesare who tried to explain how supposedly no man could murder him. Ezio then seized Cesare and threw him off the walls, leaving him to fate.
66- It's Ezio's 48th birthday in which he, Leonardo and Machiavelli discuss their plans for the future. Machiavelli informed them of a new book known as The Prince which he was writing and Leonardo explained how he will journey to France. Ezio and Machiavelli offer Leonardo a place at the Brotherhood but Leonardo declines and with this, they all say farewell and go their separate ways.
- The novel referenced to how Cesare's face had been mutilated by the "New Disease" which related to the recent outbreak of syphilis at the time - an affliction that plagued Cesare Borgia in reality - leading him to wear a mask. In the game, however, his face was always fully shown without any signs of such deformities.
- According to the novel, Cesare excelled at bullfighting. Machiavelli believed he showed such an interest in the sport due to his aggressive nature and partly being Spanish, from where the sport originated.
- It was stated by Machiavelli that Paola taught Ezio his skills in Venice, though in Assassin's Creed II, he was taught in Florence.
- In the novel, Machiavelli did not become the leader of the Italian Assassins after the death of Mario Auditore, even though his in-game database suggested so. In the novel, no new leader was elected, however, Ezio and Machiavelli both acted as chiefs. When Ezio began recruiting Assassins, La Volpe suggested that Ezio be their new leader, but he was not officially elected until the initiation of Claudia, as seen in the game.
- In the book, Ezio was a Christian, while in the game it was never alluded to.
- In the novel, Leonardo was offered a place in the Brotherhood, though he declined.
- The traitorous thief from Monteriggioni was said to be named Paganino and had once served Antonio in Venice, before being recruited by the Borgia.
- Some of Ezio's recruits were said to have wanted to go back to the normal life they once had, after the defeat of the Borgia.
- Maria Auditore passed away due to a long-time illness sometime between 1504 and 1505.
- The engineer who reinforced the Caserma d'Alviano was named Michelangelo.
- The novel went into more detail regarding Ezio's relationship and feelings for Caterina Sforza, including his distaste at being used by her.
- At the start of the novel, Mario Auditore made reference to Claudia being married and then widowed, whereas in the game, this was not mentioned.
- Pope Julius II was said to have been allied with the Assassins upon Ezio's arrival in Rome and after the fall of the Borgia. It is also mentioned that Ezio became his counselor.
- Ezio was said to have lost all of his Codex inventions at the siege of Monteriggioni, and in Rome, Leonardo rebuilt them for Ezio, as well as some additional inventions. In the game, Ezio claimed that he had lost all of the Codex inventions Leonardo had once fashioned for him, while only having lost his second Hidden Blade.
- Guns were used much more frequently by enemies in the novel; in the game they were only used by arquebusiers, Papal Guards and Cesare Borgia.
- The poison darts given to Ezio by Leonardo were not fired from Ezio's Hidden Gun like in the game, but instead they were tossed as ordinary darts.
- In the novel, it was Leonardo who constructed Ezio's crossbow for him, and Ezio only used it in one mission - while escorting Bartolomeo to "surrender" to the French army.
- Leonardo revealed that he used the Apple to locate Ezio in Rome, similarly to how Ezio discovered where Cesare was headed after his escape from prison.
- Ezio did not use the Apple as a weapon against Cesare.
- Il Carnefice, Malfatto and Silvestro Sabbatini were not mentioned at all, and Ezio did not use his recruits to assassinate any targets.
- Juan Borgia's party was not held outdoors in the Trastevere, but instead it was carried out at his own palazzo in the Vatican. Ezio did not assassinate him from a bench though, cornering him and a guard in a small room before finishing them both off instead.
- In the game, Ezio could either air assassinate the Baron de Valois or shoot him from above, though in the novel, Ezio cornered him and killed him with his sword.
- The fight between Ezio and Cesare differed slightly in the novel than in the game. They began the battle with only their fists, however, after Cesare punched Ezio, they both resorted to using swords. After disarming Cesare, Ezio parried an attack from his dagger by cutting Cesare's hand, almost severing it. Realizing his defeat, Cesare desperately shouted that he could not die by the hands of man, to which Ezio replied "then I leave you in the hands of fate!", before seizing Cesare and pushing him from the edge of the Viana castle wall, without looking down.
- Ezio and Mario both rode horses while escaping the Vatican, and they did not jump into the Tiber like what was shown in the game.
- Mario Auditore was both shot and beheaded during the defense of Monteriggioni. Afterwards, Cesare waved Mario's head at Ezio when he caught up to their escape under the tunnels, shouting "You're next!" after him.
- During the siege of Monteriggioni, Ezio was shot by Octavian de Valois, as opposed to an arquebusier in the game.
- Leonardo da Vinci was present and stood with Cesare at the siege of Monteriggioni, against his will.
- Ezio used his Apprentices to destroy Leonardo's war machines, and to guard the inventor from the Borgia. In the game, Ezio himself destroyed the constructs, and it was never mentioned that he left Leonardo with any protection.
- In the novel, the passion play and the events concerning the distrust La Volpe had for Machiavelli occurred before the assassination of Baron de Valois. In the game, the order was reversed.
- In the novel, the Thief and Courtesan missions were executed by Assassin recruits.
- The fall of the Borgia loyalists was covered in more detail in the novel.
- In 1504, Claudia Auditore da Firenze stepped down as the Madame of the Rosa in Fiore, after she was kidnapped by Borgia loyalists, while Rosa took over her position while she was absent. After Claudia was rescued, however, she returned to her role.
- Machiavelli was present when Ezio hides the Apple under the Colosseo. In the game, it is assumed Ezio is alone.
- None of the events of The Da Vinci Disappearance were mentioned.
- A more in-depth account of Ezio's hunt for Cesare was given, after the latter escaped from prison. It detailed Micheletto Corella being killed, and described Ezio's journey to Spain with Leonardo and Machiavelli, in their attempts to locate Cesare.
- In the game, all of the events, from Ezio emerging from the Vault to Cesare's arrest, took place in four years. However, due to the final scene in Assassin's Creed: Renaissance being said to have taken place in 1503 instead of 1499, these events only spanned a few months.
- None of the modern-day events were mentioned in the novel.
- In addition to the war machine designs seen in-game, a design for a kind of scythed chariot was also discussed in the novel.