Born Howard Michael Mandel on November 29, 1955, in Toronto, Ontario, Canada. The son of a lighting manufacturer and a realtor, Mandel was a class clown growing up. He was especially fond of staging pranks on friends and family. His antics got him expelled from three high schools. After earning a high school equivalency diploma, Mandel started out as a door-to-door carpet salesman. He was good at his work and grew the business, turning it into a successful retail operation with two stores. On a business trip to Los Angeles in 1979, however, his life changed forever. Mandel decided to put his comic talents to the test at the Comedy Store’s amateur night. He did well enough to impress a television producer, who hired him to appear on the comedy game show Make Me Laugh.
More offers for the rising comedic star soon followed. He served as the opening act for singer and performer Diana Ross's Las Vegas show, and eventually landed a role on the critically acclaimed drama St. Elsewhere. Debuting in 1982, the series was set at St. Eligius, a rundown urban hospital. It was one of the first shows to portray medical cases and techniques in a realistic, gritty manner. Mandel played offbeat emergency room doctor Wayne Fiscus on the series, which also featured William Daniels, Ed Begley Jr., Denzel Washington, and David Morse.