Expression levels of nucleoside diphosphate (NDP) kinase/nm23 gene product in the surgically resected 59 human pancreatic exocrine neoplasms were examined immunohistochemically using antiNDP kinase antibody. Immunoreactivity for NDP kinase varied from one tumor to the other. Out of the 47 invasive pancreatic duct cell carcinomas examined, 31 (66%) tumors showed strong immunoreactivity for NDP kinase, whereas ten (83%) of 12 benign or less invasive tumors (in situ adenocarcinoma and mucin-producing tumor) showed negative or weak immunoreactivity (p < 0.01; Chi-square test). Overall survival of invasive pancreatic duct cell carcinomas with strong immunoreactivity for NDP kinase was poorer than those with negative or weak immunoreactivity (p < 0.03; generalized Wilcoxon test). Strong immunoreactivity for NDP kinase was associated with the type of histological differentiation, the presence of lymph node metastases (p < 0.05, respectively; Chi-square test), and the number of argyrophilic nucleolar organizer regions (p < 0.01; Student's t-test). These results suggest that NDP kinase/nm23 gene product expression was positively associated with tumor aggressiveness and poor survival of patients in human pancreatic exocrine neoplasms. They also suggest that NDP kinase expression is related to cell proliferation activity represented by the number of argyrophilic nucleolar organizer regions. Therefore, examining the level of NDP kinase/nm23 gene product could serve as a marker for malignant potentiality of pancreatic exocrine neoplasms.