Breast cancer is one of the most serious problems in oncology. We investigated the antitumor potential of lycopene (Lyco) alone or combined with tocopherol (Lyco + Toco) for 90 days against a single oral dose of (50 mg/kg body weight) 7,12-dimethyl[a]benzanthracene (DMBA)-induced oxidative stress and mammary carcinogenesis in female rats. The treatment protocol started from the day immediately after DMBA administration. Results obtained indicated that there was a significant elevation in the levels of malondialdehyde (MDA) and nitric oxide (NO) in serum and breast tissues of DMBA-injected rats. The combined treatment (Lyco + Toco) group showed a potential reduction of these parameters more than Lyco alone group. The activities of superoxide dismutase, catalase, and glutathione peroxidase were found to be significantly higher when compared to rats treated with Lyco alone. In DMBA group, a positive significant correlation between NO and MDA (r = 0.92) was observed. Histopathological examination revealed the formation of tumor and angiogenesis in DMBA-induced rats and these abnormal changes were ameliorated by combined treatment with Lyco + Toco. In conclusion, these results suggested that supplementation of diet with Lyco and Toco provided antioxidant defense, with strong chemopreventive activity against DMBA-induced mammary tumors.