Propolis has been used in folk medicine for centuries due to its healing properties. Ethanolic extracts of propolis (EEP) are rich sources of phenolic acid and flavonoids. Natural phenolic compounds may exert chemoprotective activity in cancer cells due to their ability to scavenge free radicals. The aim of this in vitro study was to investigate the genotoxic and anti-mutagenic effects of the EEP on human peripheral blood lymphocytes (PBLs) and their cytotoxic potential on the human breast cancer cell line (MDA-MB-231 cells). Both cell cultures were treated with six concentrations (1, 10, 50, 100, 250 and 500 μg/ml) of EEP1 and EEP2, separately and in combination with mitomycin C (MMC). Our results show that the EEP1 and EEP2 samples of propolis after separate and combined treatments with MMC did not influence the nuclear division index (NDI). In the combined treatment, both tested EEPs significantly reduced MMC-induced micronuclei (MN) in PBLs. At 48 h after exposure of the MDA-MB-231 cell line to a combined treatment of EEP samples with MMC, the IC50 values were significantly reduced (23.79 and 19.13 μg/ml, for EEP1+MMC and EEP2+MMC, respectively, in comparison to the single treatment. In conclusion, the tested ethanolic extracts of propolis exhibited a certain level of in vitro antimutagenic activity in PBLs from healthy subjects, and anticancer activity in breast cancer cell line. The presented findings suggest that the ethanolic extracts of propolis show potential in anticancer therapeutic strategy. [Projekat Ministarstva nauke Republike Srbije, br. III41010]