Background: There is a long standing interest in the identification of medicinal plants and derived natural products for developing cancer therapeutics. Here we investigated the antiproliferative properties of Melissa officinalis (MO) from Turkey on breast cancer. Methods: MO extracts were studied for cytotoxicity against breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). In vitro apoptosis studies were performed by annexin V staining and flow cytometry analyses. Immunohistochemistry for Ki-67 and caspase 7 in the tumoral tissue sections of DMBA-induced mammary tumors in rats was also performed, along with TUNEL assays to detect apoptotic cells. In vivo anticancer activity testing was carried out with reference to inhibition of growth of DMBA induced mammary tumors in rats. Results: MO showed cytotoxicity against three cancer cell lines, inducing increase in Annexin-positive cells. Expression of caspase-7 protein and TUNEL positive cells were much higher in rats treated by MO, compared with the untreated control group, while expression of Ki-67 was decreased. Furthermore, in vivo studies showed that mean tumor volume inhibition ratio in MO treated group was 40% compared with the untreated rats. Conclusion: These results indicated that MO extrcts have antitumoral potential against breast cancer.