Malignant mesothelioma (MM) is a rare and aggressive tumor of the pleura. The most important causal factor for the development of MM is occupational exposure to asbestos. Different lines of evidence suggest a role of genetic background in MM development, as for other cancers. Two published studies observed an association between MM and N-acetyl-transferase 2 (NAT2) polymorphisms. First, a Finnish study observed that the NAT2 slow acetylator phenotype was associated with an increased risk of MM. Conversely, MM risk was higher in Italian subjects carrying the NAT2 fast acetylator genotypes. The conflicting results obtained in Finland and Italy could be ascribed to random chance, considering the small panel of patients and controls in the two studies, but also ethnic or other differences may have been important. To ascertain the role of NAT2 genotype, we performed a study on 252 MM patients and 262 controls recruited in two Northern Italy areas that were characterized by high asbestos exposure, due to intense industrial activities (an asbestos cement factory in Casale Monferrato, mainly shipyards and refineries in Liguria). Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). NAT2 fast acetylator genotypes showed an increased OR, although not statistically significant, both in asbestos-exposed subjects (OR=1.47; 95% CI=0.96-2.26) and in the entire population (OR=1.38; 95% CI=0.93-2.04). These results suggest that NAT2 polymorphisms do not exert a strong effect on individual susceptibility to MM.