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A pilot study was undertaken to test whether combining the polymerase chain reaction with restriction fragment length polymorphism is suitable for the routine diagnosis of carcinoma of the pancreas. The method makes it possible to recognize point mutations in codon 12 of the Ki-ras oncogene. 60 cytological specimens from the pancreatobiliary tract, the bronchopulmonary system (by bronchoalveolar lavage or from pleural effusion) and ascites were tested. Results from nine pancreas carcinoma cell lines served as control. A PCR product was successfully amplified in all cell lines and 47 of the clinical specimens. In all eight samples in which a mutated Ki-ras oncogene was demonstrated, there was at least a suspicion of malignancy by cytological examination. A mutation was also found in four of five pancreas carcinomas. But no mutation was found in one, clinically certain, case of pancreas carcinoma. The described method is an elegant and, most of all, rapid means to complement and optimize any cytological diagnosis.