In a 2-month-old crossbred calf with paraplegia, results of neurologic evaluation were suggestive of a spinal cord lesion caudal to L3. The calf bled from the blood sampling site for an extended period after venipuncture. Leukocytosis, anemia, and thrombocytopenia were observed. The leukocytes were predominantly atypical blast cells. Postmortem examination revealed petechial hemorrhages throughout the internal organs. Bone marrow was pale tan, with no red marrow seen. Atypical leukocytes were diffusely distributed throughout the body, with penetration of the spinal cord and spinal roots, particularly in the lumbar region. Atypical leukocytes stained positively for alpha-naphthyl acetate esterase and chloracetate esterase, and stained with Sudan black B. Atypical leukocytes expressed class-1 and class-2 major histocompatability antigens, but did not express specific T-, B-, or null-cell surface antigens. The final diagnosis was myelomonocytic leukemia. Differential diagnosis of leukemia in calves should include myelogenous leukemia, and requires use of various techniques to make a definitive diagnosis.