Abstract A 26‐year‐old, 126‐kg (277‐lb), entire, female sloth bear ( Melursus ursinus ) was evaluated following a 2‐week history of hyporexia and lethargy. Diagnostic work‐up revealed peritoneal effusion and elevated liver enzymes. Abdominal exploratory surgery revealed a firm omental mass, a focal lesion within the wall of the pyloric outflow tract and a uniformly thickened gall bladder. Biopsy results were indicative of carcinomatosis with an undetermined primary. These results along with the patient's quick deterioration led to humane euthanasia. Postmortem histopathological examination supported the diagnosis of ampullary carcinoma with carcinomatosis, extensive lymphatic invasion and lymph node, hepatic and pulmonary metastasis. Further investigation is needed to determine best diagnostic modalities and treatment options in ursids diagnosed with ampullary carcinoma. To the authors’ knowledge, this is the first documented report of carcinoma of the ampulla of Vater in an ursid.