A 4-year-old, neutered male Domestic Shorthair cat with a history of depression, anorexia, and weight loss was diagnosed with acute myelogenous leukemia (AML). The cat tested positive by both the feline immunodeficiency virus antibody test and feline leukemia virus enzyme-linked immunosorbent assay test. Results of cytochemical stains on peripheral blood and bone marrow specimens indicated acute myeloid leukemia with unusual basophilic differentiation (AML, M-2B).