In 1494, Piero de' Medici was exiled by Girolamo Savonarola, who had gained control over Florence using the Apple of Eden. Piero fled to Venice, where Savonarola's supporters were also attempting to spread Savonarola's influence.
Piero stood up to one of these heralds, causing a brawl between him and Savonarola's supporters. Piero was aided by Ezio Auditore, a friend of his late father who saved Piero from being killed by the herald. They quickly parted ways again when Ezio went to Florence to take down Savonarola's rule.
- He was a student and possible murderer of Angelo Ambrogini through the use of arsenic poisoning.