Extracellular matrix degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the extracellular matrix. HPR1 is not expressed in normal epithelial cells but can be detected in a variety of malignancies. In the present study, we examined HPR1 expression in pancreatic cancer by using in situ hybridization and tested whether HPR1 expression correlated with any clinicopathlogic parameters. HPR1 was not detected in the ductal cells of normal pancreas samples obtained from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99 pancreatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex, tumor stage, and lymph node status were not predictive of HPR1 expression. Log-rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in early-stage tumors was associated with decreased survival. HPR1 expression was frequent in pancreatic adenocarcinomas and was associated with decreased survival in early-stage tumors. This suggests that HPR1 may contribute to the highly invasive and early metastatic behavior of pancreatic cancer.