The product of the nm23-H1 gene, reported to be a metastatic suppressor gene, was recently identified as the nucleoside diphosphate (NDP) kinase A, and was found to be overexpressed in several types of malignant tumors as compared with normal tissues. In order to determine whether NDP-kinase expression serves as a marker for metastatic potential and whether hyperproliferation of neoplastic cells would correlate with expression, we analyzed NDP-kinase levels and activity by immunohistochemical staining and by an enzymatic assay in 13 benign and 98 malignant breast-tissue specimens. Our results confirm that NDP-kinase expression increases in malignant cells of breast carcinomas, but cannot be considered as a biological marker of metastatic dissemination. No correlation was found between NDP-kinase activity and S phase, taken as an index of cell proliferation. Moreover, no correlation was observed between NDP-kinase activity and tumor size, histoprognostic index, estrogen receptors or progesterone receptors. The mechanism of over-expression of NDP in malignant cells and its role in tumor progression remain to be determined.