Breast cancer is a complex pathology related to endocrine disorders. Its occurrence in aged women is due to exposition to endocrine disruptors, such as bisphenol A (BPA), during windows of susceptibilities of mammary development. Also, estrogenic exposition and treatment are commonly employed to control peri-menopausal side effects, which could implicate neoplastic development. However, natural compounds with estrogenic activity impact the responses of the mammary gland (MG), considering these substances as potential cancer-prevent molecules. We aimed to evaluate the histopathological repercussions of phytoestrogen therapy with genistein (GIN) in MG of aged gerbils under pro-carcinogenic endocrine disruption. Thus, Mongolian gerbil females (N=30) were exposed to BPA in two windows of susceptibility for MG (pregnancy and lactation) to induce the onset of mammary carcinogenesis at aging. At 12 months of age, they were subdivided into two groups: EDC – females only exposed to endocrine disruption; GIN – females treated with genistein (240 mg/kg/day for 6 months). The control group was performed without any treatment. The females were euthanized at 18 months of age, and MG was collected for histopathological analysis. Histological and immunohistochemistry were used to detect alterations in the epithelial compartment. [Ethical approval: CEUA IBILCE, Protocol number 235/2022.]. GIN phytotherapy promoted the decrease of ductal carcinoma in situ (DCIS) incidence (11.31% ± 3.8) in MG compared to only EDC exposition (26.13% ± 6.4). Although, hyperplasia (55.83% ± 7.68) and microinvasive carcinoma (2.96% ± 1.15) were observed in this group, in which hyperplastic structures were highly enhanced in GIN treatment. CD117 positive cells, a marker for luminal mammary cells, were decreased compared to the control group (Control: 98.13% ± 1.3; GIN: 79.7% ± 5.74), but not in comparison with EDC (81.8% ± 7.95). Also, p63-positive basal cells apparently were restored and enhanced by GIN treatment (16.62% ± 6.9), since EDC and control presented low values (9.08% ± 1.47; 7.40% ± 2.61, respectively) for nuclear p63-positive cells. Basal reprogramming, a pro-invasive feature observed by cytoplasmatic p63, was reduced in the MG of the GIN group (19.58% ± 6.93), which is a characteristic of EDC carcinogenic induction. An imbalance in proliferation and cell death was observed. GIN treatment promoted a diminished proliferative activity by phospho-histone H3 positive cells (7.39% ± 3.0), in comparison with the EDC group (14.59% ± 2.11), but not with control MG (3.42% ± 2.22). Also, caspase 3 activity was measured for apoptotic activation, analyzing their isoforms inactive (iCASP3) and active/cleaved (cCASP3). Control MG presented enhanced apoptosis by elevated cCASP3 positive cells (15.6% ± 5.1) compared to other groups and to iCASP3 (6.99% ± 1.87), as well as in the GIN group that presented a slight enhancement (8.43% ± 2.21) compared to iCASP3 (6.69% ± 1.47). Bcl-2, an antiapoptotic switch, was decreased in GIN treatment (1.23% ± 0.67) in comparison to EDC (2.75% ± 0.81), corroborating with the results of the caspase cascade. GIN treatment mitigates the effects of carcinogenesis induced by the endocrine disruptor BPA. By restoring basal cells and reducing disordered proliferation, GIN phytotherapy activated bcl-2/caspase 3 mechanisms to induce apoptosis to delay neoplastic development in the MG. Thus, GIN presents as a protective therapy minimizing the pro-malignant effects of endocrine disruption.