BACKGROUND/AIMS: Intraductal papillary mucinous tumors (IPMTs) of the pancreas contain a wide spectrum of histopathologic abnormalities ranging from hyperplasia to adenocarcinoma. Unlike ductal adenocarcinomas of the pancreas, the genetic alterations in the evolutionary stages of neoplasia in IPMTs are still obscure. The aim of this study was to determine genetic alterations of K-ras, p53, and p16 in various stages of IPMTs. METHODS: Eighteen patients (M:F=14:4; mean age, 59 years) were diagnosed as having IPMT by ERCP and pancreatectomy from 1991 to 1998. Genomic DNA was extracted from the paraffin embedded tissue sections after microdissection. The presence of K-ras mutation was determined by restriction fragment length polymorphism method. Expressions of p53 and p16 were determined by immunohistochemistry. RESULTS: No mutations were found in any sites with normal histologic findings. K-ras point mutations were detected in 22%, 83% and 86% of hyperplasia, adenoma, and adenocarcinoma, respectively. Also, we found overexpression of p53 in 8%, 67% and 67%, and deletion of p16 in 15%, 20% and 50% of hyperplasia, adenoma and adenocarcinoma, respectively. CONCLUSIONS: These three genetic mutations, known to be involved in the carcinogenesis of ductal adenocarcinomas of the pancreas, may play an important role in the carcinogenesis of IPMT of the pancreas.