We describe a case of atypical acute promyelocytic leukemia (APL) with a tetraploid clone and multiple karyotypic abnormalities in addition to the translocation (15;17)(q22;q21). Microscopically, the leukemic cells were highly heterogeneous in morphology and granularity, being bizarre and large in size compared with classical APL blasts. The patient responded to treatment with chemotherapy and all-trans-retinoic acid, at diagnosis and at relapse 10 months later. He is currently in clinical and molecular remission, 3 years after initial diagnosis. Tetraploidy in association with large and bizarre blasts has not been previously reported in APL. Although tetraploidy and complex karyotypic aberrations confer a poor prognosis in other types of acute myeloid leukemia, in the presence of t(15;17) they did not appear to affect the prognosis, inasmuch as the clinical features and treatment outcome in our case followed those of APL in general.