One of the longstanding challenges in the treatment of pancreatic cancer, the fifth most common cancer worldwide, is to establish a simple and reliable diagnostic marker for the disease. This study examined whether or not the plasma levels of IgG antibodies (IgGs) reactive to peptides derived from the prostate stem cell antigen (PSCA), which is highly expressed in pancreatic cancer cells, were elevated in patients with pancreatic cancer. Fifty-seven kinds of peptides encoded by PSCA were tested for their reactivity to plasma IgGs of pancreatic cancer patients. The results showed that the levels of IgGs specific to each of the 10 different peptides in the plasma of pancreatic cancer patients were significantly higher than those of non-cancer subjects. Eighty percent of subjects with and 18% of subjects without pancreatic cancer were diagnosed as having pancreatic cancer, respectively, when those cases showing significantly elevated levels of IgGs against at least one of the three peptides of PSCA at positions 2-11, 85-95, and 109-118 were judged as positive for pancreatic cancer. These results indicate that the measurement of IgGs reactive to these PSCA-derived peptides can provide novel information on the host-tumor interaction in pancreatic cancer, and could potentially be used as a new diagnostic tool to screen for pancreatic cancer.