To understand the underlying mechanisms in myelodysplastic syndromes (MDS) by identifying target tumor suppressor genes, we performed a detailed deletional mapping of the short arm of chromosome 1 in 38 paired samples of bone marrow and peripheral blood obtained from individuals with MDS by PCR amplification of a total of 23 highly informative microsatellite sequences. We identified the commonly deleted region between D1S508 and D1S244. LOH of this region was found in five patients (13%). In addition, LOH at 1p was associated with a poor clinical outcome, suggesting that the deletion of a gene in this region may be involved in the course of this disease. By analyzing the chromosomal map of this region, we found TNFRSF12 as a candidate tumor suppressor gene. However, our search for mutations in this gene did not identify somatic mutations in MDS. Our findings are consistent with the possible existence of an as-yet unknown tumor suppressor gene in this region that is altered in MDS.