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Inzerillo was born in Palermo. He married Giuseppa Di Maggio, the daughter of his mother’s brother, Rosario Di Maggio – the boss of the Passo di Rigano Mafia family. Through a string of marriages the Inzerillo’s were related to the Di Maggio and Spatola families in Palermo and the Gambino’s in New York. He had two sons, Giuseppe and Giovanni.
Inzerillo was a close ally of Stefano Bontade and Gaetano Badalamenti and a relative of the New York City Mafia boss Carlo Gambino. He became a member of the Sicilian Mafia Commission in 1978 succeeding his uncle Rosario Di Maggio, and formed a strong alliance with Bontade against the growing power of Totò Riina and the Corleonesi who were increasingly challenging the established Mafia families of Palermo.
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Salvatore Inzerillo ordered the killing of prosecuting judge Gaetano Costa who signed the 53 arrest warrants against the Spatola-Inzerillo-Gambino clan and their heroin-trafficking network in May 1980. Costa was murdered on August 6, 1980. Inzerillo acted without asking permission from the Mafia Commission to prove he could commit a murder in rival territory (that of Giuseppe Calò) just as the Corleonesi.
On May 11, 1981, Inzerillo was gunned down in Palermo as he strolled towards his recently acquired bullet-proof car after leaving the house of his mistress. He was rendered almost unrecognizable by a hail of bullets from a machine gun. The firearm used was an AK-47, the same gun that killed Bontade the previous month. The deaths of these two powerful mafiosi kick-started the Second Mafia War that lasted almost two-years and saw hundreds of mafiosi killed as Totò Riina and the Corleonesi decimated their rivals in order to take over Cosa Nostra by sheer brute force.
It is believed Inzerillo was murdered by Pino Greco, one of Riina's most lethal hitmen. At Inzerillo's funeral, his teenage son Giuseppe vowed to avenge his father, and not long afterwards the boy was kidnapped, tortured and killed. A number of informants, including Tommaso Buscetta, said that it was Pino Greco who abducted the youth and shot him through the head, but first hacked his arm off, symbolically removing the arm the youngster had vowed to shoot Riina with.