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Concern about the genotoxic risk associated with chronic handling of antineoplastic drugs has increased, and usual safety practices may not avoid exposure.Comet assay and MN test were performed on 30 oncology nurses and 22 controls. Genetic polymorphisms of XRCC1, XRCC3, and APE1 genes were determined by PCR-RFLP.Data obtained showed increased cytogenetic and DNA damage in the exposed group, although statistical significance was only reached in the comet assay. Significant differences in TL were observed for carriers of the variant alleles of every gene analyzed. However, no significant effect was detected in the MN test.Evidence that the present handling practices of antineoplastic drugs in some Portuguese hospitals are not enough to prevent exposure are provided. Present data suggest that genetic polymorphisms in the studied DNA repair enzymes may influence the individual susceptibility to DNA damage related to chronic handling of antineoplastic drugs.