Genetic heterogeneity influencing enzyme activity may change the capacity to repair DNA damage induced by environmental and endogenous factors. This study aims to assess the impact of Lys751Gln (A/C) polymorphism in the XPD gene, encoding an enzyme involved in the nucleotide excision repair pathway, on individual DNA damage. The DNA damage in human lymphocytes (% DNA in the tail) was quantified by means of single-cell gel electrophoresis. Baseline levels of DNA damage significantly differ between AA homozygotes and carriers of the C allele, and the observed differences were not related to age, gender, or smoking status. It seems that the AA variant is associated with enhanced protection against oxidative DNA damage.