Malfatto was an infamous serial killer of members of the courtesan faction in Rome. He became feared enough to catch the attention of Cesare Borgia, Who recruited him into his underground army.
In 1502 Cesare sent his envoy, Fiora Cavazza, to deliver a needed Letter of Absolution to Malfatto to gain his alliance. Although Fiora hesitated, being a courtesan herself, she nonetheless searched for Malfatto.
During her first attempt to search for Malfatto, Fiora searched through the Poor District of Rome. but Instead of finding Malfatto, Fiora heard the sounds of a Courtesan Woman Crying and begging for her life. Fiora ran to find the victim of Malfatto, but she arrived too late and found the latest bloody victim of Malfatto dead. After this, Fiora started to refuse Cesare's orders of find the doctor, but obeyed when Cesare made a threat to have her killed. Going Dressed in one of her old courtesan outfits as to lure Malfatto to her, Malfatto attacked Fiora, but she only narrowly dodged.
The doctor only paused only when Fiora started yelling out Cesare's name at him and showed him the letter she had been tasked to deliver. Malfatto took it without a word, however did not read it. He watched the Courtesan Fiora walk away.
In panic, Fiora instinctively grabbed her bladed fan to defend herself, Much to Malfatto's shock as he isn't used to his victims fighting back. Despite being under the effects of the poison Malfatto had injected her with, she managed to wound the doctor severely, but the poison got the best of her and she fell unconscious. being very wounded, Malfatto escaped through Fiora's window and got away
When the Assassin found Malfatto by a medical stall, the murderer started fleeing, with Ezio in close pursuit. After a short chase, Ezio called his assassin apprentices in for the assassination. As Malfatto lay dead, Ezio held a hand over his mask and offered him his last rites.
In the multiplayer mode, the Animus training program run by Abstergo uses Malfatto's personality to create the persona of The Doctor. When making a kill, he uses a long syringe to stab targets and inject them with a unidentified green poison. In most low profile kills he goes for the neck, and in some cases the eye when face to face. Other than his appearance and preferred method of assassination, he plays exactly the same as the other multiplayer persona.