Two chimeric genes, PML-RAR-alpha and RAR-alpha-PML, are formed as a consequence of the acute promyelocytic leukemia (APL)-specific reciprocal translocation of chromosomes 15 and 17 [t(15;17)]. PML-RAR-alpha is expressed as a fusion protein. We investigated the organization and expression pattern of the RAR-alpha-PML gene in a series of APL patients representative of the molecular heterogeneity of the t(15;17) and found (i) two types of RAR-alpha-PML mRNA junctions (RAR-alpha exon 2/PML exon 4 or RAR-alpha exon 2/PML exon 7) that maintain the RAR-alpha and PML longest open reading frames aligned and are the result of chromosome 15 breaking at two different sites; and (ii) 10 different RAR-alpha-PML fusion transcripts that differ for the assembly of their PML coding exons. A RAR-alpha-PML transcript was present in most, but not all, APL patients.