In 1503, Cesare Borgia ordered Micheletto Corella to poison Pietro Rossi, because he was jealous of Pietro's relationship with Lucrezia. As Pietro was playing Jesus Christ in the Passion Play held at the Colosseo, Micheletto placed cantarella into the wine fed to Christ during his crucifixion. Despite this, Pietro was saved by Ezio Auditore da Firenze, who quickly brought him to a doctor, Brunelleschi.
Later that same year, in August, Lucrezia Borgia ordered a shipment of cantarella to be delivered to the Castel Sant'Angelo, though her intentions for it were unknown. The following day, Rodrigo Borgia secretly took the shipment for himself.
On the 18th of August 1503, Rodrigo Borgia attempted to poison his own son Cesare with cantarella concealed within an apple, after Cesare abused his position as Captain General of the Papal army. Cesare did not consume a lethal amount of the poison however, but it did render him ill for months after.
Following Rodrigo's attempt to poison his son, Cesare force-fed him the same cantarella-filled apple, resulting in his death.
- Both in the game as well as in the novelization, it was mentioned by the doctor who cured Pietro Rossi that in addition to the antidote, leeches would ensure full recovery.
- In the novel it was further elaborated that the doctor, Brunelleschi, had developed an effective antidote due to experience with numerous victims of the poison.
- It is generally assumed by historians that cantarella was simply a variation of arsenic. On the other hand, its actual historical use by the Borgias - and even its very existance - have been doubted by others.