A 20-year-old mule was evaluated for anorexia and fever. Haematological evaluation revealed a population of large, immature lymphoid cells and significant anaemia. Bone marrow aspiration was unsuccessful, and abdominal ultrasonographic evaluation was unremarkable. The mule was subjected to euthanasia due to poor prognosis, and necropsy and histological evaluation revealed multicentric B cell lymphoma. The leukaemic phase of lymphoma is rarely documented in equids, and is regarded as an indication of advanced or aggressive disease. To the authors' knowledge, lymphoma in a mule has been reported only once previously.