Deletions of DNA on chromosome 9p21-22 are frequently observed in cells derived from melanomas, gliomas, non-small cell lung cancers, and acute lymphoblastic leukemia. The minimal deletion shared by the latter three cancers extends from the interferon-alpha locus towards the centromere; its centromeric end is flanked by the gene encoding methylthioadenosine phosphorylase. We have determined that the telomeric end of the minimal homozygous deletion shared by two melanoma cell lines does not include the methylthioadenosine phosphorylase locus. Thus, a distinct region of DNA is lost in melanoma. The physical size of this region remains to be defined precisely, but it may extend over several million base pairs.