Abstract: To compare the cell proliferation and apoptosis in normal breast tissues, precancerous lesions of the breast, and breast cancer tissues of TA2 mice as well as to ascertain the effects of mitochondrial apoptosis pathway on the oncogenesis of spontaneous breast cancer in TA2 mice by detecting the expression of Bcl-2, Bax, Caspase-3, and Caspase-9 proteins in the breast tissues during the mitochondrial apoptosis pathway. Methods: Normal breast tissues were obtained from adult female TA2 mice ( NC ). Precancerous breast tissues ( SBC-b ) and breast cancer tissues (SBC-t) were obtained from female TA2 mice with spontaneous breast cancer. PCNA, Bcl-2, Bax, Caspase-3, and Caspase-9 expression was determined by immunohistochemistry, whereas cell apoptosis was determined by TUNEL assay. Proliferation (PI) and apoptosis (AI) indices were calculated. The relative expression of Bcl-2, Bax, caspase-3, and caspase-9 mRNA and protein were determined by real-time PCR and Western blot. Results: Immunohistochemistry, real-time PCR, and Western blot assays indicated that the AI, PI, and the expression of Bcl-2, Bax, caspase-3, and caspase-9 mRNA and protein were higher in the SBC-b group compared with those in the NC group ( P < 0.01 or P < 0.05 ). The expression of all proteins, except for Bcl-2, was significantly lower in the SBC-t group compared with that in the NC group ( P < 0.01 ). However, the expression of bcl-2, bax, and caspase-3 mRNA was evidently higher in the SBC-t group, compared with that in the NC ( P < 0.01 ). The expression of caspase-9 mRNA was slightly higher in the SBC-t than in the NC, which was not statistically significant ( P > 0.0 5). Conclusion: Mitochondrial apoptosis pathways may contribute to the genesis of spontaneous breast cancer in TA2 mice by inducing the apoptosis of mammary epithelium as well as by destroying the balance of proliferation and apoptosis in mammary epithelium.