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Mancuso is an Italian surname derived from a Sicilian noun, related to the Italian mancino, which means "left-handed". An alternate form can be Mancusi. Notable people with the surname include:

• Adolfo Mancuso (born 1930), Argentine swimmer
• Alejandro Mancuso (born 1968), Argentine footballer
• Anna Mancuso (born 1971), Canadian politician
• Ciro Mancuso (born 1949), Nevada-based drug dealer convicted of running a $140-million marijuana smuggling operation
• David Mancuso (1944–2016), American DJ
• Eros Mancuso (born 1999), Argentine footballer
• Filippo Mancuso (1922–2011), Italian judge and politician
• Francis Xavier Mancuso (1887–1970), leader of Tammany Hall and judge for New York's Court of General Sessions
• Frank Mancuso Jr. (born 1958), movie producer
• Gianluca Mancuso (born 1998), Argentine footballer
• Gus Mancuso (1905–1984), catcher in Major League Baseball from 1928 to 1945
• Julia Mancuso (born 1984), American alpine skier who won a gold medal at the 2006 Winter Olympics
• Laurence Mancuso (1934–2007), founding abbot of the New Skete monastery
• Leonardo Mancuso (born 1992), Italian footballer
• Matteo Mancuso (born 1996), Italian jazz and rock guitarist and composer
• Nick Mancuso (born 1948), Italian-Canadian cinema and stage actor
• Renee Mancuso, American bridge player
• Rudy Mancuso (born 1992), American actor and Internet personality and musician
• Salvatore Mancuso (born 1964), Colombian paramilitary warlord
• Stefano Mancuso (born 1965), Italian botanist and writer

In fiction

• Angelo Mancuso in the novel A Confederacy of Dunces (1980) by author John Kennedy Toole
• Bart Mancuso, played by Scott Glenn in the film The Hunt for Red October (1990)
• Nick Mancuso, played by Robert Loggia in the television miniseries Favorite Son (1988) and the television crime series Mancuso, F.B.I. (1989)

• Surnames
• Italian-language surnames
• Surnames of Italian origin
• Surnames of Argentine origin