The NME1 gene, localized to human chromosome 17 at q22, shows reduced expression in tumors of high metastatic potential. A homologous gene, NME2, with similar reduced expression in breast carcinoma, has recently been reported. We have isolated and characterized five yeast artificial chromosome (YAC) clones and three cosmid clones that contain both genes, demonstrating that the NME2 gene is also located on chromosome 17 and is separated by not more than 18 kb from the NME1 gene. The two putative tumor suppressor genes, encoding the two polypeptide chains of nucleoside diphosphate (NDP) kinase, are thus quite close to each other on chromosome 17, indicating that they may well have arisen by a tandem duplication. Both genes now appear to be excluded as candidates for the early-onset breast cancer (BRCA1) locus.