When the Kingpin (Wilson Fisk) was absent from New York for a long period of time, Fortunato stepped into the power vacuum and, using his Hydra ties, was able to force the other crime-lords, such as the Slug and Hammerhead, into accepting him as the new kingpin.

His elder son Giacomo (better known as Jimmy-6) is present at the meeting where Fortunato portrays his power. The Don brings out the killer Tombstone to be executed. Then he brings out random civilians from each of the crime-lord's territories. The plan is to have each crime-lord kill a civilian, showcasing how Fortunato would punish disobedience by civilian massacres.

Jimmy 6, horrified, pulls a gun on his father in front of the crowd of people. The spectators do not intervene, wishing to see how Fortunato would handle this. Ben Reilly (then Spider-Man), intervenes, soon joined by Daredevil. The innocent civilians are freed but they and the heroes are cornered, pursured by various members of the meeting. Jimmy-6 shows up in an attack helicopter, killing the pursuers and rescuing the civilians and the superheroes. Jimmy eventually reconciles with his father, but extends his debt to Ben to Peter Parker.

Fortunato's dominance was eventually shattered when the Kingpin returned, launching a massed simultaneous attack on New York's crime-lords and taking command during the confusion. The assassin Nitro attacks Fortunato on the Kingpin's orders, leaving him comatose. Jimmy Six was seen leading his organization for several months afterward. Later, the elderly Fortunato re-emerged and bought the Venom Symbiote at an auction for his younger son, the awkward 18-year-old Angelo. Angelo attempts to use the suit to kill Spider-Man, but the symbiote rejects him as unworthy and allowed him to fall to his death. It was also confirmed that Jimmy-6 had somehow made peace with his Father, as Fortunato briefly referred to him as "My Beautiful Giacomo", showing no signs of ill will. With Angelo dead, Jimmy-6 is in all probability the sole heir to Fortunato's crime empire.