Since human CYP2A13 is expressed in the respiratory tract and is involved in the activation of tobacco-specific nitrosamines, some of the previously reported sequence variations may contribute to inter-individual and inter-ethnic differences in the susceptibility of tobacco-related tumorigenesis. The aim was to compare the frequencies of the 578C > T (Arg101Stop), 3375C > T (Arg257Cys) and 7520C > G (3'-untranslated region) mutations in several populations. The frequencies of the 578C > T polymorphism were 3.8, 0 and 1.0% in French Caucasians, Gabonese and Tunisians, respectively. In the same populations, the frequencies of the 3375C > T mutation were 0, 15.3 and 4.2%, respectively, whereas the frequencies of the 7520C > G mutation were 1.0, 20.8 and 7.3%, respectively. Marked inter-ethnic variations in CYP2A13 were identified and confirmed. These findings provide data for further studies that associate CYP2A13 haplotypes with an incidence of smoking-related tumours in respect of ethnicity.