An ultrastructural study was performed in four patients with acute myeloid leukemia (AML) and 8;21 translocation. The most prominent pathologic features of the leukemic cells were: (1) a high frequency of nuclear blebs, which have been associated with an aneuploid karyotype; (2) nucleocytoplasmic asynchrony in early myeloid precursors, mature polymorphonuclear leucocytes (PMN) and in megakaryocytes; (3) abnormal granule formation with the presence of Auer rods, giant granules (pseudoChediak-Higashy) containing small vesicles, primary granules, and rod-like structures; absence of secondary granules in the more mature myeloid cells and the presence of hypogranular forms; (4) the presence of "labyrinths" consisting of myeloperoxidase (MPO) negative circular tubuli, interwoven with MPO positive endoplasmic reticulum; (5) the lack of hiatus leukemicus. Although none of these features separately is pathognomonic for 8;21 AML, we can conclude that the combination of these ultrastructural findings characterizes the leukemic myeloid cells of patients with 8;21 translocation in AML.