His assassination at the hands of distant cousin Lorenzaccio caused the title of Duke to pass to Cosimo I de Medici, from the family's junior branch.

[5][6][7][8][9][10] Some historians, such as Christopher Hibbert, present two hypotheses as to Alessandro de Medici's ancestry: he was "rumoured to be Cardinal Giulio's son by either a Moorish slave or a peasant woman from the Roman Campagna".

[12] French author Jean Nestor reported in the 1560s that the claim of a Moorish slave origin was a false rumor first spread by Alessandro's exiled enemies in Naples.

[13] University of Florence historian Giorgio Spini too described this rumour as unfounded, instead tracing Alessandro's mother to a peasant from the Roman countryside who would later go on to marry a carrier from Lazio.

[14] Alessandro spent his early childhood in Rome, where he received a humanist education by Pierio Valeriano Bolzani, under the supervision of Pope Leo X and Cardinal Giulio de’ Medici.

Clement’s choice increased tension between the Medici cousins; for the rest of Ippolito’s life, he spoke openly about wanting to overthrow Alessandro and lead Florence.

[28] While Clement lived, Alessandro ruled "with the advice of elected councils, trying to calm the nerves of the defeated republicans"; however, as his reign progressed he showed authoritarian tendencies.

His “common sense and his feeling for justice won his subjects’ affection”; and he “enjoyed some status as the champion of the poor and the helpless, as ballads and novelle record.”[25][16] He was also a patron of the arts, commissioning notable works by Giorgio Vasari, Jacopo Pontormo, Benvenuto Cellini, and Antonio da Sangallo the Younger.

[34] After the exiles voiced their complaints to Charles, Florentine diplomat Francesco Guicciardini responded, “his Excellency’s virtue, his fame, the opinion of him held throughout the city, of his prudence, of his virtuous habits, are a sufficient reply".

Eventually, Alessandro succumbed to his wounds and Lorenzino and Scoronconcolo fled from the palace – after locking the door to the chamber to prevent their crime from being discovered too quickly.

"[33][24] For fear of starting an uprising if news of his death became public, Medici officials wrapped Alessandro's corpse in a carpet and secretly carried it to the cemetery of San Lorenzo, where it was hurriedly buried.