The glutathione S-transferase M1 (GSTM1) gene is polymorphic in humans, and the deficiency in enzyme activity of GSTM1 is caused by the inherited homozygous absence of the GSTM1 gene, or the "null" genotype (GSTM1, 0/0). The increased risk of bladder cancer has been shown to correspond with this gene defect. No reports, however, have been found in the literature regarding GSTM1 gene deficiency with superficial and invasive bladder cancer. In this study, we examined the association of the GSTM1-null genotype with superficial and invasive bladder cancer. Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the GSTM1 gene defect in Turkish patients with superficial bladder cancer (N = 61), invasive bladder cancer (N = 42), and control subjects (N = 202) who had no history of cancer. The GSTM1 null genotype was observed in 34.7% of the control subjects and in 54.3% of total bladder cancer patients (OR: 2.246; 95% CI: 1.384-3.645, P: 0.00094). In other words, the presence of the GSTM1-null genotype significantly increased the risk of bladder cancer development. Among invasive bladder cancers, the frequency of the GSTM1-null genotype was 64.3% (OR: 0.294, 95% CI: 0.147-0.590, P: 0.0003). This was also significantly higher than control subjects, indicating that patients carrying this genotype were at increased risk for developing invasive bladder cancer. This relationship was not statistically significant in the superficial bladder cancer group (OR: 0.585, 95% CI: 0.327-1.045, P: 0.06). Our results indicate that GSTM1 gene polymorphism should be considered as an important risk modifier in the development of bladder cancer and might be used as a predictive marker for invasive bladder cancer.