Two functional polymorphisms within the manganese superoxide dismutase (MnSOD) gene have been reported to lead to increased oxidative stress damage. The MnSOD 58T > C single nucleotide polymorphism (SNP) within exon 3 changes isoleucine to threonine, leading to decreased thermal stability and reduced enzymatic activity in vivo and in vitro. The MnSOD 60C > T polymorphism within exon 3 changes leucine to phenylalanine, rendering the protein sensitive to redox regulation by intracellular thiols. Thus, the goal of this study was to evaluate the 58T > C and 60C > T MnSOD polymorphisms in a large case-control study. Taqman allelic discrimination assays were developed to identify the 58T > C and 60C > T SNPs in exon 3. Two hundred and eight lung cancer cases and 141 controls were evaluated for these two SNPs, and all 349 subjects were of the wild-type homozygous genotype for both 58C and 60T in exon 3. This study suggests that although the 58T > C and 60C > T polymorphisms reduce MnSOD enzymatic activity, these polymorphisms were not identified in the present case-control study population.