Punica granatum L. (Punicaceae) whole fruit extracts, have been used in Cuban traditional medicine as an effective drug for the treatment of respiratory diseases. This species showed interesting anti-viral activity, e.g. aqueous or hydroalcoholic extracts of whole fruits have proved highly active against the influenza virus. However, some toxic properties of this extract have also been reported and, to date, very little is known about its genotoxic properties. In the present study, the genotoxicity of a Punica granatum (pomegranate) whole fruit extract was assessed using different in vitro and in vivo assays that detect DNA damage at different expression levels. Results from reversion and gene-conversion test in microorganisms, sister chromatid exchanges, micronuclei and sperm-shape abnormality assays in mice, clearly showed that the hydroalcoholic extract of P. granatum whole fruits is genotoxic when tested both in vitro and in vivo.