Abstract CASE DESCRIPTION A 14-year-old 120-kg (264-lb) sexually intact male Sumatran tiger (Panthera tigris sumatrae) and its 10-year-old 130-kg (286-lb) sexually intact male offspring were housed separately and evaluated independently after experiencing weeks of ongoing malaise, weight loss, and anorexia. CLINICAL FINDINGS Both animals were immobilized and anesthetized for physical examinations and diagnostic testing. Complete blood counts revealed leukopenia and anemia in both tigers. Splenomegaly was identified on abdominal ultrasonography. Cytologic examination and immunohistochemical staining of splenic samples confirmed intermediate to large B-cell lymphoma; no evidence of lymphoma in surrounding organs was noted. TREATMENT AND OUTCOME The sire was treated with lomustine and prednisolone. This tiger was euthanized 21 months after initiation of treatment because of chronic progressive renal disease. The male offspring was treated with l-asparaginase but did not respond to the treatment. A splenectomy was performed, and malaise and anorexia resolved. No further chemotherapy was administered, and the male offspring was instead maintained on a low dose of prednisolone. Thirty-two months after diagnosis, the male offspring was still considered to be in remission. CLINICAL RELEVANCE To our knowledge, this was the first known report of the diagnosis and management of a splenic B-cell lymphoma in a tiger. Both tigers achieved positive clinical responses and long-term survival by means of different treatment modalities. The finding of such an unusual neoplasm in a male tiger and its male offspring was noteworthy, raising the possibility of a genetic predisposition for this lymphoma type.