The Cannaregio district, being a large district located at the north of Venice, was the residential district of the city. It later became a ghetto for the Jews of Venice in 1516.
On June 25, 1488, a group of Borgia guards returned from their journey to Cyprus and arrived at the Arsenal Shipyard in the Castello District. One of the guards took the Apple of Eden which they had taken from Cyprus and brought it to Rodrigo Borgia in Cannaregio. However, the guard was intercepted by the Assassin Ezio Auditore en route to the rendezvous with Rodrigo, and was subsequently killed by Ezio, who disguised himself as the guard and met with Borgia instead. Upon meeting the Cardinal, Ezio quickly revealed himself and fought him. Ezio was soon joined by his uncle, and several other of his friends, who unbeknownst to Ezio, were Assassins. The group triumphed over Cardinal Borgia and his guards and claimed the Apple for themselves, though they failed to kill Rodrigo, who escaped.