- "I feel the world flying by and I need to catch it, to become part of its tides and currents."
- ―Michelangelo, in a letter to his father.[src]
In the message, Michelangelo revealed that he had abandoned his schooling almost a week previous, as he had "felt the world flying by," and desired to be a part of it. He stated that he wanted to live up to his father's expectations, but also asked for his blessing to become an artist, an occupation his father greatly disapproved of.
At that time, Domenico Ghirlandaio had just invited Michelangelo to join him as an apprentice, and Michelangelo praised the "masterful work" he had done in the Sistine Chapel, wishing he would be able to see it one day.
By 1511, Michelangelo had become a good friend of Ezio Auditore. In 1515, Michelangelo wrote a letter to Ezio, informing the retired Mentor about a Templar plot in Florence. Ezio sent his two apprentices, Hiram Stoddard and Giovanni Borgia, to meet with Michelangelo and to learn what their ally had discovered.
Upon learning that the Templars had found an Apple of Eden, the Assassins and Michelangelo decided to set an ambush on Dei Petrucci, the Templar who carried the artifact. However, the two apprentices failed and Petrucci fled with the Apple. Later, while in a tavern as Petrucci was still nowhere to be found, Stoddard and Borgia clashed over their failure and Michelangelo tried his best to appease the tension between the two rivals.
- Michelangelo is represented in the Artists mnemonic set in Assassin's Creed: Project Legacy.
- Though developers commented on the iconic experience of freerunning past Michelangelo's fresco on the Capella Sistina ceiling, it was not present within the timeframe of Assassin's Creed II, and so it was not included.