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- Tom Hanks as Joe "NY152" Fox
- Meg Ryan as Kathleen "Shopgirl" Kelly
- Parker Posey as Patricia Eden
- Jean Stapleton as Birdie Conrad
- Greg Kinnear as Frank Navasky
- Steve Zahn as George Pappas
- Heather Burns as Christina Plutzker
- Dave Chappelle as Kevin Jackson
- Dabney Coleman as Nelson Fox
- John Randolph as Schuyler Fox
- Deborah Rush as Veronica Grant
- Hallee Hirsh as Annabel Fox
- Jeffrey Scaperrotta as Matthew Fox
- Cara Seymour as Gillian Quinn
- Peter Mian as "The Capeman"
- Sara Ramirez as Rose
- Jane Adams as Sydney Ann
- Michael Badalucco as Charlie
- Veanne Cox as Miranda Margulies