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| Piper Perabo | Rachel |
| Jamie Lee Curtis | Aunt Viv |
| Drew Barrymore | Chloe |
| George Lopez | Papi |
| Andy Garcia | Delgado |
| Paul Rodriguez | Chico |
| Cheech Marin | Manuel |
| Manolo Cardona | Sam Cortez |
| Placido Domingo | Monte |
| Edward James Olmos | El Diablo |
| Loretta Devine | Delta |
| Michael Urie | sebastian |
| Luis Guzmán | chucho |
Chloe, a pampered Chihuahua from Beverly Hills, gets an unwelcome taste of the real world when she gets lost in a tough part of Mexico. With no Rodeo Drive boutiques in sight, she is out of her element, until scrappy street dogs Delgado and Papi lend her a paw, helping her find her way home.
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