AbstractThenm23gene, a putative metastasis suppressor gene, was originally identified by its reduced expression in highly metastatic K‐1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines. Transfection ofnm23cDNA has been reported to suppress malignant progression inDrosophilaand mammalian cells. Highly conserved homologues ofnm23have been found in organisms ranging from the prokaryoteMyxococcus xanthustoDrosophila, where the gene is involved in normal development and differentiation. The product of thenm23gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its apparent biological functions. We review recent cellular, genetic, biochemical and X‐ray crystallographic data to formulate and evaluate hypotheses concerning the molecular mechanism ofnm23act