Utilizing the polymerase chain reaction (PCR), we studied the presence and pattern of mutations in the Kirsten (Ki)-ras oncogene, using paraffin-embedded sections of pancreatic carcinoma tissue from 53 patients. Mutations in the Ki-ras oncogene were evident in 46 of the 53 patients (87%) in codon 12. The predominant mutation was from glycine (GGT) to aspartic acid (GAT). Among the 46, one had an additional mutation in Ki-ras codon 13, and no mutation was found in codon 61. These oncogenetic mutations were observed even in early stage pancreatic carcinoma, and there was no statistically significant difference in the rate or positivity of mutations among the stages of the disease. With regard to patient survival, statistical analysis comparing 37 patients with mutations in the Ki-ras oncogene and four patients without mutations revealed no significant difference. These results suggest that mutations in the Ki-ras oncogene may be related to the initiation of carcinogenesis, but are not linked to malignant potential or promotion of human pancreatic cancer.