The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (CYP2D6) and lung cancer is controversial. Previous reports suggested a link between CYP2D6 phenotype and lung cancer, with poor metabolizers having reduced susceptibility. Nevertheless, negative findings have also been published. By using allele-specific amplification, we have studied the frequency of four CYP2D6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are underpresented among patients with lung cancer because of a different genetic background. Our findings also reveal that the rare CYP2D6(C) mutant allele is sixfold more frequent among patients with lung cancer (p < 0.0005). This suggests that the CYP2D6(C) allele could be considered as an additional risk factor because carriers could have higher susceptibility to the development of lung cancer.