He committed his first murder at the age of 12,[citation needed] and was twice banished from the city of Florence for his unruly behaviour, including involvement in the rape of a sixteen-year-old boy, Giovanni being about thirteen at the time.

The following year Leo X allied with Emperor Charles V against King Francis I of France to regain Milan, Parma and Piacenza; Giovanni was called in under the command of Prospero Colonna, defeating the French at Vaprio d'Adda in November.

The League's captain general, Francesco Maria I della Rovere, abandoned Milan in the face of the overwhelming superiority of the Imperial army led by Georg von Frundsberg.

Pietro Aretino, an eyewitness to the event, recalled in a letter to Francesco Albizi: 'Not even twenty' Giovanni said smiling 'could hold me', and he took a candle in his hand, so that he could make light onto himself, I ran away, and shutting my ears I heard only two voices, and then calling, and when I reached him he told me: 'I am healed', and turning all around he greatly rejoiced.Despite the surgery, Giovanni de' Medici died five days later, supposedly of sepsis, on 30 November 1526.

[5] Giovanni's premature death metaphorically signalled the end of the age of the condottieri, as their mode of fighting (which emphasized armoured knights on horseback) was rendered practically obsolete by the introduction of pike-armed infantry.

His lasting reputation has been kept alive in part thanks to Pietro Aretino, the Renaissance author, satirist, playwright and "scourge of the princes", who was Giovanni's close friend and accompanied him on some of his exploits.