Cutaneous mast cell tumors (MCTs) are common canine neoplasms. Some dog breeds more frequently develop MCTs, suggesting a genetically mediated predisposition. In humans, the most common inherited cancer predisposition is caused by germline defects in the mismatch repair (MMR) genes. To investigate whether inherited defects in the MMR genes predispose some dogs to MCT development, MMR expression in 22 MCTs from young and predisposed breed dogs was compared with MMR expression in 22 MCTs from old dogs of non-MCT-predisposed breeds. MMR expression was investigated immunohistochemically using antibodies against MLH1, MSH2, and MSH6. Mast cells within all MCTs expressed MLH1, MSH2, and MSH6. There were no significant differences in the intensity of immunoreactivity or the percentage of cells expressing MMR proteins between MCTs from the 2 groups of dogs. There were no significant differences in MMR protein expression between grade II and grade III MCTs. These results do not support the hypothesis that inherited MMR defects predispose some dogs to MCT development.