In 1477, La Volpe (English: The Fox) was informed that Ezio Auditore da Firenze, the son of the late Assassin Giovanni Auditore da Firenze, was returning to Florence to assassinate the Templar Francesco de' Pazzi. Ezio was told by his friend, Leonardo da Vinci, that La Volpe would be able to assist him with this matter. Upon hearing this, Ezio searched for La Volpe in the Mercato Vecchio.
Whilst looking for the legendary rogue, a thief quickly pickpocketed Ezio and fled. Ezio was able to catch up with him, but as he demanded his money back, La Volpe appeared and gave the money back to him, saying that he was willing to aid him if the Assassin could keep up with his free-running skills. La Volpe then led Ezio to the Santa Maria Novella, where the Pazzi conspirators were to convene later that day.
La Volpe waited for Ezio near to the sewers, from where he would later emerge after eavesdropping on the Templar meeting. Ezio informed him that they were planning to kill the Medici during High Mass, in order to claim Florence for themselves, and install their politicians in charge. La Volpe replied that it would be disastrous if Lorenzo de' Medici were to be killed, as he was a powerful ally of the Assassins, though Ezio assured him that he would not allow him to die.
In 1488, La Volpe and the other Assassins from Florence met in Venice to acquire the Apple of Eden from Rodrigo Borgia, the Grand Master of the Templar Order. When they arrived at Rodrigo's location, they saw him fighting with Ezio Auditore, and promptly intervened to help Ezio defeat him and his men. Eventually, Rodrigo fled, and left the Apple behind with the Assassins. After answering many queries from Ezio, they proceeded to induct him into the Assassin Order, with each member (including La Volpe) performing a Leap of Faith afterwards.In 1494, Florence was taken over by Girolamo Savonarola, who had stolen the Apple from Ezio after an incident in Forlì.
La Volpe and the others gathered once more to witness Savonarola's execution, though Ezio reconsidered, and decided that he should not have to suffer the pain and humiliation of being burned alive in front of a crowd of people. Thus he hurried towards the flames, and assassinated him before he began to burn. He then gave a speech, and, looking towards the other Assassins, approvingly spoke of how he been guided to his own path by "a few strangers."
In 1499, La Volpe gathered with the same Assassins he had met with in Venice in the Villa Auditore in Monteriggioni to unveil the location of the Vault. Through the Codex pages, they discovered that the Vault was located in Rome, and that it was in fact the true reason that Rodrigo Borgia had become Pope, as he could obtain the Staff of Eden. They then traveled to Rome, where they created a distraction for the Borgia forces, while Ezio infiltrated the Sistine Chapel.
After the Assassins returned from Rome, Monteriggioni was besieged by the Borgia, and as a result, the Assassin Mario Auditore was killed by Cesare Borgia. After this, some members of the Assassin Order, including La Volpe, traveled to Rome to dispose of the Borgia's influence there. When Ezio found him in Rome, he was the leader of a Thieves Guild, just as he had been in Florence, but unlike in Florence, he refused to cooperate with Niccolò Machiavelli, calling him a traitor to the Assassin cause.
La Volpe believed that Machiavelli had betrayed them and had sided with the Borgia, since Machiavelli had left Monteriggioni the night before the siege, as well as later stating that he suspected him of being behind an attack on the Roman Thieves Guild. However, Ezio later found the real traitor at the Colosseum, who happened to be a thief that stayed back at the Siege of Monteriggioni, and quickly rushed off to keep La Volpe from killing Machiavelli. Ezio arrived just in time to inform him of the situation, and when La Volpe realized he was mistaken, he immediately concealed his weapon and grew warmer to an oblivious Machiavelli, greeting him as a friend and ally.
La Volpe was also present during Claudia Auditore's induction into the Assassin Order, and the battle against Cesare's remaining followers before his arrest.