During the early 1980s, Mancuso was an associate of the Purple Gang. In 1984, Mancuso fatally shot his wife Evelina and left her body on a bench in front of Jacobi Hospital. Mancuso plead guilty to manslaughter and served ten years in prison.
In 2004, acting boss Vincent Basciano promoted him to the acting underboss position. He became acting boss in November 2004, after Basciano was imprisoned. In May 2005, Joseph Massino implicated Mancuso in the 1999 murder of Gerlando Sciascia. In early 2006, Vincent Basciano ordered Mancuso's murder.
On February 16, 2006 Mancuso was arrested for ordering a 2004 murder. Mancuso and imprisoned Basciano ordered the November 30, 2004 murder of Bonanno associate Randolph Pizzolo the hit was carried out by soldier Anthony "Ace" Aiello. On August 6, 2008 Mancuso and soldier Aiello pled guilty to murdering Pizzolo. On December 16, 2008 Mancuso was sentenced to 15 years and soldier Aiello was sentenced to 30 years in prison.
Mancuso is currently imprisoned at the Federal Correctional Institution, Edgefield with a projected release date of March 12, 2019.
In June 2013, Mancuso while imprisoned for the next five years was picked as the new official boss of the family. He is first mobster in the family to hold this title since boss Joseph Massino became a government witness in 2005. Currently Mancuso's underboss Thomas DiFiore is running the family on the streets.