An approach to detect K-ras oncogene mutated at codon 12 was devised by using a nested polymerase chain reaction strategy based on mismatched primers. A titration experiment showed that the sensitivity obtained by use of the nested PCR was 1/512. This represented the ability to detect one cell heterozygous for K-ras codon 12 mutation over 500 normal cells and was 100-fold greater than that obtained after one-step PCR. Application of this assay to 9 patients with adenocarcinoma of the lung showed 5 cases containing one or more K-ras mutation at codon 12. It is suggested that the method was practicable and worthy of application and dissemination.