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- Jack Nicholson as Melvin Udall
- Helen Hunt as Carol Connelly
- Greg Kinnear as Simon Bishop
- Jill the Dog as Verdell
- Cuba Gooding, Jr. as Frank Sachs
- Julie Benz as the Receptionist
- Shirley Knight as Beverly Connelly
- Jesse James as Spencer "Spence" Connelly
- Skeet Ulrich as Vincent Lopiano
- Yeardley Smith as Jackie Simpson
- Lupe Ontiveros as Nora Manning
- Harold Ramis as Dr. Martin Bettes
- Danielle Spencer as The Veterinarian