Glutathione S-transferase (GST) activity is believed to play a critical role in cellular protection against toxic chemicals. We evaluated the role of GSTM1 polymorphisms in modifying the association between indoor pesticide exposure and cutaneous melanoma. Peripheral blood samples were collected from 325 individuals (177 patients with cutaneous melanoma and 148 controls). Genotyping was performed using the PCR method. Participants were interviewed to collect data on pesticides used indoors, sociodemographic characteristics, medical history, sun exposure and pigmented characteristics. Odds ratio and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. After adjustment for sex, age, education, hair colour, skin photo-type, solar lentigines, number of nevi and sunburns episodes in childhood, a 2.76-fold (95% CI: 1.08-7.08) increase in the risk of cutaneous melanoma was observed for GSTM1 null individuals highly exposed to indoor pesticides (≥2 times/year) in comparison with GSTM1 active individuals who received low exposure (<2 times/year). Participants exposed to these products for 10 years or more and with GSTM1 null genotype also had an increased risk of cutaneous melanoma (odds ratio: 2.78; 95% CI: 1.01-7.66) in comparison with participants with a low duration of exposure (<10 years) and active GSTM1. These findings suggest that the GSTM1 null genotype is a risk modifier for cutaneous melanoma.