A deletion of the long arm of chromosome 20 [del(20q)] is a recurring abnormality in malignant myeloid disorders. The occurrence of the del(20q) in a broad spectrum of myeloid disorders suggests that the loss of genetic material on 20q could provide a proliferative advantage to myeloid cells, possibly through the loss of a tumor-suppressor gene. We have examined a series of patients with the del(20q) using fluorescence in situ hybridization (FISH) with unique sequence probes that map along the length of 20q, and have delineated a segment that is deleted in 95% of all patients examined (18 of 19). In addition, we have shown that the deletions are interstitial rather than terminal. This region of deletion extends from 20q11.2 to q12, and is flanked by the RPN2 (proximal) and D20S17 loci (distal). The SRC and ADA genes are located within the commonly deleted segment. Our findings emphasize the importance of FISH and other molecular mapping techniques in defining such a region. The delineation of a commonly deleted segment in 20q11.2- q12 will facilitate the identification of candidate tumor-suppressor genes on 20q.