To clarify whether scattered endocrine cells in pancreatic ductal adenocarcinoma are neoplastic or not, we immunohistochemically studied 29 cases of invasive pancreatic ductal adenocarcinomas, 17 with metastases, for chromogranin A, insulin, glucagon, pancreatic polypeptide, serotonin, gastrin, laminin, and Ki-67. Endocrine cells were found in primary sites in 24 cases (82.3%), where endocrine cells showed at least a visibly close location to adjacent islet cells. Although endocrine cells in neoplastic glands were within the neoplastic basement membrane, endocrine cells were not seen in invasive sites beyond the pancreas where islets were not present. Endocrine cells in neoplastic glands were reactive for two or three of the islet hormones in all cases, and different types of hormonal reactivity was recognized in the same neoplastic gland or the same cluster of neoplastic glands in 22 (91.7%) cases, thus suggesting a close relation with islets. Ki-67 did not stain any endocrine cells in ten of the adenocarcinomas studied. In three (10.3%) cases, endocrine cells were found in the intraductal extensions. They may have pre-existed in non-neoplastic ducts. In 17 cases with metastatic sites, all but one had no endocrine cells in the metastases. Serotonin-positive cells were found in one metastatic lymph node in one case. We concluded that most endocrine cells seen in ductal adenocarcinomas of the pancreas are non-neoplastic and are derived from the surrounding islets. Some neoplastic endocrine cells may exist, though their frequency is low.