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- Guy Pearce as Leonard Shelby
- Carrie-Anne Moss as Natalie
- Joe Pantoliano as Teddy
- Mark Boone Junior as Burt
- Russ Fega as Waiter
- Jorja Fox as Leonard's Wife
- Stephen Tobolowsky as Samuel R. Jankis
- Harriet Sansom Harris as Mrs. Jankis
- Thomas Lennon as Doctor
- Callum Keith Rennie as Dodd
- Kimberly Campbell as Blonde
- Marianne Muellerleile as Tattooist
- Larry Holden as James F. Grantz