A 4-yr-old, captive-bred, male veiled chameleon (Chamaeleo calyptratus) presented with anorexia, weight loss, and stomatitis. Complete blood count revealed pancytopenia and a marked leukocytosis (197 × 10³/µL) composed of blast cells (195 × 10³/µL) that had oval to irregular nuclei with finely stippled chromatin and occasional nucleoli. The diagnosis was acute leukemia of presumptive myeloid origin. Treatment with prednisone (1.5 mg/kg once daily orally) and cytosine arabinoside (300 mg/m² subcutaneously) was initiated. Post treatment hematologic analysis revealed decreased blast count (88.5 × 10³/µL) and improved mentation. Additional doses of cytosine arabinoside were given 2 and 3 wk after the initial diagnosis with marked improvement in circulating blast concentration (15.3 × 10³/µL). During the course of treatment, which included the chemotherapeutics, fluid therapy, and oral supportive care, the chameleon's weight increased 32.5% (199–295 g). Unfortunately, the animal died 33 days after presentation. Histopathologic evaluation revealed hypocellular bone marrow with rare, blast-like cells within vessels and mycotic granulomatous hepatitis with intralesional hyphae and fructiferous bodies. The blast cells expressed Iba1 but not CD3, CD79a, or lysozyme, suggesting a myeloid origin. Cell morphology further reinforced an acute myeloid leukemia. The authors surmised that the chameleon was responding to treatment, but ultimately succumbed to the mycotic hepatitis. This report describes the first case of acute myeloid leukemia with response to chemotherapeutic intervention in a veiled chameleon.