Complex variant 15;17 translocations are increasingly recognized in acute promyelocytic leukemia (APL). We report the case of a 47-year-old woman with APL harboring a novel four-way translocation. She presented with persistent bleeding after a tooth extraction. Blood cell counts at admission were hemoglobin at 9.0 g/dL, platelets at 15 x 10(9)/L, and white blood cells at 0.460 x 10(9)/L with abnormal promyelocytes. Most nucleated cells of bone marrow aspirates were abnormal promyelocytes with Auer rods. Chromosome analysis of unstimulated bone marrow cell cultures revealed a variant t(15;17) in the form of t(10;17;15;22)(q22;q21;q22;q11.2). Fluorescence in situ hybridization with a PML/RARA dual-color DNA probe showed the fusion signals on der(15) and the residual PML signals on der(22). RT-PCR showed long-form PML/RARA fusion transcripts. A complete remission was attained with a course of conventional chemotherapy including ATRA. A literature review revealed that our case is one of the very rare four-way translocations and the first report of the involvement of chromosomes 10 and 22 in a variant t(15;17).