Background: Breast cancer, major threat worldwide, even with a variety of treatment approaches, the death rate is still high. Argemone mexicana, traditionally used in several conditions, experimentally, plant extract showed anti-microbial, antioxidant, cytotoxic, and anti-cancer properties. There was lack of reports regarding its anticancer activity in-vivo. Aim: This study is aimed at investigate anticancer properties of Argemone mexicana leaves (AML) extract against MNU-induced mammary tumors by comparing the tumor volume, external features and histopathological results of the experimental groups. Methodology: Experimental rats divided into 4-groups: Group I-normal control, Group II-tumor control (MNU alone, 50 mg/kg/b.w.), Group III-treated with 500 mg/kg/b.w. of AML, and Group IV- treated with Tamoxifen (TAM) 10 mg/kg/b.w. Treatment were started immediately nest to tumour induction. After the experimental period, collected mammary tumor mass, calculated weight and volume of the tumor, and compared external features and histopathological studies. All data were analyzed by Students t-test and results were statistically significance (P˂0.05). Results: Tumor weight and volume were reduced in AML and TAM-treated groups compared to tumor control. External features were observed in tumour control rats, tumor mass under growing beneath the skin, deep wound with ulcerated skin compare to treated rats. Microscopic studies revealed that there was cellular improvement and fewer pleomorphic changes in extract-treated groups, like TAM-treated rats, compared to MNU-treated rats. There was severe infiltration of hyperchromatic and pleomorphic nuclei in tumour induced rats. In rats treated with MNU-induced AML, there was a large rise in the expression of caspase-3 and Bax proteins, but a significant decrease in PCNA and, Bcl-2 protein expression. The aforementioned proteins' expression is restored after AML treatment. Conclusion: From the results, Argemone mexicana leaf extract might have antitumor/anticancer activity by reducing tumor volume, and showing improvement in external features and under microscope. But isolation and identifying individual compounds for anticancer properties can be continued as extended activities.