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. We summarize here the clinical histories, and gross and histologic findings of 12 American pikas, including 9 captive (wild-caught) and 3 wild animals. Death was often attributed to stress (transport, handling, anesthesia) with few-to-no premonitory clinical signs. Infection was the cause of death in 2 cases: 1 had bacterial pyogranulomatous dermatitis, cellulitis, and lymphadenitis with sepsis; the other case had oomycete-induced necrotizing colitis. Incidental parasitic infections included sarcocystosis, nematodosis (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 that periportal hepatic lipidosis is non-pathologic in American pikas. Three cases had myocardial necrosis that was considered the cause of death; the cause of necrosis was not determined, but it may have been caused by 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 can result from lack of mucosal abrasion by ingesta. Several histologic findings that are likely normal in American pikas include splenic extramedullary hematopoiesis, thymic tissue in adults, and Clostridium sp. in the enteric lumen.