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.