ERCC2 and ERCC1 are important in DNA nucleotide excision repair and lie on chromosome 19q13.3 near a putative glioma suppressor region. We genotyped constitutive variants ERCC1 C8092A and ERCC2 K751Q and R156R in approximately 450 adults with glioma and 500 controls from two independent population-based series, uniformly reviewed patients' tumors to determine histopathologic category, and determined a variety of tumor markers among astrocytic tumors. Odds ratios (ORs) for glioblastoma for those carrying two ERCC1 A alleles versus none or one were 1.67 in series 1 and 1.64 in series 2, which yielded a combined OR of 1.67 (95% CI, 0.93-3.02; P = 0.09), adjusted for age, gender, ethnicity, and series. Odds ratios for the ERCC2 variants were not consistently elevated or reduced for the two series in all cases versus controls. However, among whites, for those with ERCC2 K751Q genotype QQ versus QK/KK, the OR for nonglioblastoma histologies versus controls was 1.82 (95% CI, 0.97-3.44; P = 0.06). Also, among whites, glioma patients were significantly more likely than controls to be homozygous for variants in both ERCC1 C8092A and ERCC2 K751Q (OR, 3.2; 95% CI, 1.1-9.3). Given the numbers of comparisons made, these findings could be due to chance. However, the results might warrant clarification in additional series in conjunction with the nearby putative glioma suppressor genes (GLTSCR1 and GLTSCR2).