Acquired interstitial deletions of the long arm of chromosome 5, are seen in anomalies of the myeloid cells. The refractory anemia (RA) or 5q- syndrome, in which the erythroid and megakaryocytic lineages are predominantly affected, is a relatively indolent clinical entity distinguishable, from the constellation of preneoplastic myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) with trilineage involvement. Recent molecular evidence suggests that the critical region of 5q deletion in MDS/AML resides in the D5S89 locus, which is proximal (centromeric) to the minimal region of loss in the 5q- syndrome RA. The invariable loss of the D5S89 locus in MDS/AML qualifies it for the MDS/AML tumor suppressor locus. The telomeric 5q31 gene governs erythroid and megakaryocytic differentiation and can be termed the RA locus. Isolation and characterization of these genes will lead to an understanding of molecular mechanisms underlying normal hematopoiesis and leukemic transformation.