Several members of the transmembrane 4 superfamily (TM4SF) have been reported to be related to tumor progression and metastasis. The aims of our study were to clarify the relationship between TM4SF and pancreatic cancer and to determine the prognostic significance of TM4SF in human pancreatic cancer. The mRNA levels for MRP-1/CD9, KAI1/CD82 and ME491/CD63, which belong to the TM4SF gene family, were evaluated in 40 resectable pancreatic adenocarcinomas using reverse transcriptase-PCR. MRP-1/CD9 gene expression was associated with lymph node status, and with pathological status. Moreover, MRP-1/CD9 expression was inversely associated with histo-pathological grading. KAI1/CD82 gene expression was inversely associated with tumor status. ME491/CD63 gene expression, however, was conserved in all pancreatic cancers. The overall survival rate for the 22 patients whose tumors had decreased MRP-1/CD9 gene expression was strikingly lower than that for the 18 patients with MRP-1/CD9-positive tumors. The overall survival rate of the 15 patients who were KAI1/CD82-positive was significantly higher than that of the 25 patients with decreased KAI1/CD82 gene expression. In a multivariate analysis using the Cox proportional hazards model, MRP-1/CD9 and KAI1/CD82 status was found to be the most significant.