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- Ben Stiller as Mr. Furious
- William H. Macy as The Shoveler
- Hank Azaria as The Blue Raja
- Kel Mitchell as Invisible Boy
- Paul Reubens as The Spleen
- Janeane Garofalo as The Bowler
- Wes Studi as The Sphinx
- Geoffrey Rush as Casanova Frankenstein
- Eddie Izzard as Tony P.
- Prakazrel Michel as Tony C.
- Artie Lange as Big Red
- Lena Olin as Dr. Anabel Leek
- Greg Kinnear as Captain Amazing
- Ricky Jay as Victor Weems
- Tom Waits as Dr. A. Heller
- Claire Forlani as Monica
- Dane Cook as The Waffler
- Doug Jones as Pencil Head
- Dana Gould as Squeegee Man
- Michael Bay as Frat Boy
- Riki Rachtman as Frat Boy
- Goodie Mob as The Not-So-Goodie Mob
- Cee Lo Green as The Not-So-Goodie Mob
- Monet Mazur as Becky Beaner
- Louise Lasser as The Blue Raja's Mother
- Angelica Bridges