A 7-year-old spayed Louisiana Catahoula Leopard dog was examined to determine the cause of shifting forelimb lameness, anorexia, and lethargy. The dog was pyrectic and had splenomegaly, thrombocytopenia, and nonregenerative anemia. Examination of a bone marrow aspirate revealed hypocellularity with normal maturation of erythroid and granulocytic cell lines; however, approximately half of the cells were large undifferentiated blast cells. These cells were identified as megakaryoblasts, using immunohistochemical techniques to detect reactivity for Factor VIII-related antigen and platelet glycoprotein IIIa. Necropsy revealed diffuse neoplastic involvement of the spleen, liver, lungs, bone marrow, and lymph nodes. Cellular infiltrate was characterized by a mixture of megakaryoblasts and typical megakaryocytes. Megakaryoblastic leukemia (M7) is the designation proposed by the Animal Leukemia Study Group for myeloproliferative neoplasms of megakaryocytic lineage.