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He debuted on Broadway in Working (1978). He also helped write Bleacher Bums, an award-winning play, which was first performed at Chicago's Organic Theater Company. He won a Tony award for his portrayal of Richard Roma in David Mamet's play Glengarry Glen Ross.

He made his feature film debut in Medusa Challenger (1977). He played womanizing dentist Bruce Fleckstein in Compromising Positions (1985). Other early movies include co-starring roles in The Money Pit (1986), Weeds (1987) and Suspect (1987). He also starred in the critically acclaimed movies House of Games (1987) and Things Change (1988), for which he and co-star, Don Ameche, both received the Best Actor Award at the Venice Film Festival. In 1991 he starred in the highly praised police thriller Homicide. A highly versatile actor, Mantegna has played a wide range of roles, from the comic - as a fed up shock jock in Airheads and the hilariously inept kidnapper from Baby's Day Out to the dramatic, in roles such as Daysor Joey Zasa, a treacherous mobster in The Godfather Part III.

Mantegna also has a recurring role in the animated series The Simpsons as the voice of mob boss Anthony "Fat Tony" D'Amico.

On August 11, 2007, Mantegna signed on to replace departing star Mandy Patinkin on the CBS crime drama Criminal Minds.

(wikipedia.org)