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| John C. Reilly | Dewey Cox |
| Jenna Fischer | Darlene |
| Raymond J. Barry | Pa Cox |
| Kristen Wiig | Edith Cox |
| Tim Meadows | Sam |
| Harold Ramis | L'Chai'm |
| Margo Martindale | Ma Cox |
| Chris Parnell | Theo |
| Matt Besser | Dave |
| John Michael Higgins | Record Producer |
| Conner Rayburn | Young Dewey Cox |
| Paul Rudd | John Lennon |
| Jason Schwartzman | Ringo Starr |
| Justin Long | George Harrison |
| Jack White | Elvis Presley |
| David Krumholtz | Schwartzberg |
Following a childhood tragedy, Dewey Cox follows a long and winding road to music stardom. Dewey perseveres through changing musical styles, an addiction to nearly every drug known and bouts of uncontrollable rage, until finally, he wins the heart, but not necessarily the body, of his loyal backup singer, Darlene .
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