Seven cases of pancreatic serous cystadenoma were examined immunohistochemically and molecular biologically. Six were benign tumors and one was clinically malignant. Immunohistochemical studies were performed with the avidin-biotin peroxidase complex technique on paraffin-embedded tumor tissue and were stained with antibody to carcinoembryonic antigen (CEA), CA19-9, and p53 protein. Two-stage polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect K-ras oncogene mutation at codon 12. No tumor cells were stained with anti-CEA and anti-p53 protein, but two cases were stained focally with anti-CA19-9. One case was benign and one was clinically malignant. In the anti-CA19-9 staining, tumor cells of the benign case were positive only on the apical membrane and supranuclear cytoplasm of the cells, whereas those of the clinically malignant case were positive over the entire surface and cytoplasm of the cells. All seven cases were without K-ras gene mutation. So the features of serous cystadenoma of the pancreas suggest a tumor genesis different from that of ductal adenocarcinoma. They also suggest a relationship between immunohistochemical localizations of CA19-9 in the tumor cells and the biological behavior of the tumor itself.