This is the first study to evaluate the potential genotoxicity of p,p′-DDT (1, 1, 1-trichloro-2,2-bis-(chlorophenyl)ethane) and its metabolites (p,p′-DDD and p,p′-DDE) in the sentinel mollusc Zebra mussel (Dreissena polymorpha). DNA damage was measured using the single cell gel electrophoresis (SCGE) assay and the micronucleus test (MN test), which represent two of the more sensitive biomarkers for genotoxicity evaluation. Three different concentrations (0.1, 2, and 10 μg/L) of each compound were administered in water for 168 hr, maintaining mussels at constant laboratory conditions and collecting several specimens every 48 hr for biochemical analyses. At the same time, the bioaccumulation process and the concentration/effect relationship were checked by GC-MS/MS analyses of mussel soft tissues. The SCGE assay results showed a clear and significant (P < 0.05) relationship between DNA injuries and tested doses for all the homologues throughout the 7-day exposure period. The final DNA damage due to p,p′-DDE was almost double that of the other two homologues that showed the same toxicity pattern. The micronucleus frequency analysis confirmed the genotoxicity potential of the three homologues and p,p′-DDE showed the highest irreversible DNA damage. The capability of Zebra mussels to biotransform the administered compound in the other homologues was demonstrated by multiple regression analyses carried out between the MN frequencies and the concentrations of the different homologues in the mussel soft tissues. A greater genotoxic potential of the p,p′-DDE with respect to the other two chemicals was revealed.