RETINOIC acid is a vitamin A derivative with striking effects on development and cell differentiation^1–3. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized^4–8 and indirect evidence suggests that they have distinct roles^9–11. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions^12–13. Because the RARα gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21–qll–22) translocation specifically associated with APL¹⁵, we analysed RARα gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RARα gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RARα fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RARα and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor α in leukaemogenesis.