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Conclusion: The present study suggests that Ki-raspoint mutations may play an important role in the early stages of tumorigenesis and that a double mutation has a stronger detrimental effect than a single mutation on the survival after pancreatectomy. Background: Previous studies have suggested the important role of Ki-raspoint mutations inrasgene codon 12 in the tumorigenesis of pancreatic cancer, but their clinicopathological significance is still unclear. The present study was designed to assess the clinicopathological significance of Ki-raspoint mutations, and p21 expression in malignant and benign diseases of the pancreas. Methods: Oligonucleotide dot-blot hybridization for Ki-raspoint mutations in codon 12 and immunohistochemical staining for p21 expression were applied. Cases included 44 primary and 15 metastatic lesions of pancreatic cancer, and 17 benign pancreatic diseases. Results: Ki-raspoint mutations and p21 expression were detected in 43 and 19 primary lesions, 9 and 6 metastatic lesions, and four and five benign diseases, respectively. The patients with a single mutation had a better survival after pancreatectomy than those with a double mutation. The patients with a p21(+) GAT mutation showed the worst survival after pancreatectomy compared with other categories of patients.