Abstract: The most frequent chromosomal rearrangement reported in acute promyelocytic leukemia (APL) is t(15;17)(q22;q21). The t(15;17) generates the PML/RARA fusion gene that blocks the transcription of genes involved in myeloid cell differentiation. A small number of simple and complex variants of the classical t(15;17) have been reported. We report two complex three-way translocation variants, t(3;17;15)(q27;q21;q22) and t(8;17;15)(q24.3;q12;q22) in which the PML/RARA fusion gene has been created on the derivative 15 chromosomes. Many of these variant translocations are suspected by conventional cytogenetics but need to be confirmed with additional molecular testing. We discuss the importance of supplementing conventional cytogenetic testing with FISH and RT-PCR to accurately diagnose APL variant patients.