To date, few tumors have been identified in prairie dogs, with odontoma being the most common. Osteosarcoma has been documented in a wide range of species, including a number of rodents. In this case, a locally invasive maxillary osteosarcoma was diagnosed in a prairie dog. Gross examination revealed a pale, tan, lobulated, sessile maxillary mass extending ventrally into the oral cavity from the hard palate and the gingiva surrounding the upper right cheek teeth. The mass invaded the right nasal cavity and retrobulbar space causing exophthalmia. Microscopically, the mass consisted of densely packed spindle-shaped cells with occasional multinucleated giant cells. Brightly eosinophilic osteoid was multifocally scattered in the tumor mass. To the authors' knowledge, this is the first documented report of maxillary osteosarcoma in a prairie dog.