A 46-year-old white male presented with a two-week history of a flu-like illness and bleeding gums. A diagnosis of acute promyelocytic leukemia was made on bone marrow examination with accompanying DIC. All cytogenetically abnormal cells (28/30 at intake and 30/30 at two weeks post-induction) represented a single clone with apparent deletion of 1(p22) and 3(p25), and with a large, derivative chromosome 17. By conventional G- and C- banded analysis, the monocentric der(17) appeared to be disrupted distal to the typical (17q21) APL breakpoint, chromosome 15 did not demonstrate gross rearrangement, and the source of the additional material on the der(17) was unknown. Fluorescence in situ hybridization (FISH) with t(15;17), RAR alpha, and 17qter probes and with chromosome 1, 15, and 17 paints demonstrated that the der(17) consisted of a complex rearrangement with duplication of both RAR alpha and PML, insertion of chromosome 1 sequences, and double insertion of chromosome 15 sequences. The fusion of RAR alpha and PML consistent with APL appears to have occurred at the distal juxtaposition of these sequences in the derivative chromosome.