The correlation between clinicopathologic findings and point mutation in codon 12 of c-Ki-ras gene was examined in primary lung adenocarcinomas using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in ten of 67 cases (15%). Microscopically, mutation-positive cases revealed a tendency to be well differentiated (P less than 0.01). Especially, the incidence of the mutation-positive cases was significantly higher in goblet cell type (three of four) than in other types (five of 56) (P less than 0.001). None of 21 cases of pure Clara cell type showed the mutation (P less than 0.05). The mutation was detected frequently in tumors with no lymph node metastasis (P less than 0.05), with larger tumor size (P = 0.01), and T2 cases (P less than 0.01). Cigarette smoking was not always a contributing factor for mutation. This study revealed that the point mutation of c-Ki-ras codon 12 in lung adenocarcinoma has been associated with the cytologic subtype.