American pikas (Ochotona princeps) are small lagomorphs that live in mountainous talus areas of western North America. Studies on the histopathology of American pikas are limited. This report summarizes the clinical histories, and gross and histologic findings of 12 American pikas, including nine captive and three wild animals. Death was often attributed to stress (transport, handling, and anesthesia) with few to no premonitory clinical signs. Two cases died due to infection: one had bacterial pyogranulomatous dermatitis, cellulitis, and lymphadenitis with sepsis; the other case had fungal necrotizing colitis. Incidental parasite infections included sarcocystosis, nematodiasis (oxyurids), and ectoparasitism. Most animals with adequate nutritional status had periportal hepatic lipidosis. This finding was absent in all animals with adipose atrophy, and it is possible periportal hepatic lipidosis is non-pathologic in American pikas. Three cases had myocardial mineralization that was considered the cause of death; the cause for mineralization was not determined, but may have been due to stress or vitamin E/selenium deficiency. Esophageal hyperkeratosis was noted in animals with a history of anorexia and negative energy balance. Accumulation of esophageal keratin may have been caused by lack of mucosal abrasion associated with ingestion. Several histologic findings that are likely normal in American pikas include splenic extramedullary hematopoiesis, thymic tissue in adults, and Clostridium in the enteric lumen.