Distributions of sialylated derivatives of Lewis a (Le^a) antigen in cancer tissue of the human pancreas and in the sera of patients with pancreas diseases have been studied; the significance of 2‐3 and 2‐6 sialylation of Le^a antigens in pancreas cancer have been investigated using specific monoclonal antibodies. In most pancreas cancer tissue the 2‐3 sialylated Le^a antigen was found to be specifically distributed in cancer cells as determined by immunohistologic techniques, while a significantly smaller amount of the antigen was detected in surrounding nonmalignant pancreas tissue, which was infiltrated by cancer cells. Conversely, the 2‐6 sialylated Le^a antigen was abundantly present in nonmalignant pancreas tissue, while it was less frequently present in pancreas cancer cells. When the sera of 66 patients with pancreas diseases were examined for these sialylated Le^a antigens, correlation studies showed that the levels of 2‐3 sialylated Le^a tended to be 44.1 times more than the levels of 2‐6 sialylated Le^a in the sera of cancer patients. The average ratio of 2‐3 sialylated Le^a to 2‐6 sialylated Le^a was 0.23 in the sera of patients with pancreatitis. These data collectively indicate that the 2‐3 sialylation of Le^a is remarkably enhanced, and the 2‐6 sialylation of Le^a antigen is suppressed in pancreas cancer. The determination of the 2‐3 sialylated Le^a to 2‐6 sialylated Le^a ratio in patients with pancreas diseases may be helpful for the differential diagnosis of pancreas cancer and nonmalignant pancreatic disorders.