Purpose <p>Phosphatase and tensin homolog (PTEN) is a tumor-suppressor gene, and that gives rise to several cancers as a result of mutations. We aimed to evaluate the histopathological, predictive, prognostic, and therapeutic importance of PTEN gene in breast cancer using in silico analysis tools. </p> Methods <p>Genomic alterations in the PTEN gene were detected using TCGA datasets via cBioPortal. Histopathological analyses were conducted from patient tissue images retrieved from cBioPortal and the Human Protein Atlas. Predicted responses to treatment were analyzed by means of ROC Plotter. </p> Results <p>PTEN gene was found in myoepithelial (&lt;25%) and ductus cells (25-75%) in the breast tissue of healthy individuals. The mutation, deletion, and structural variation of this gene led to breast cancer at a rate of 8%, most commonly in the form of invasive ductal carcinoma (IDC) (42.2%). All breast cancers resulting from the PTEN gene led to structural impairments and infiltration in cells and tissues (≥75%), and pathological changes were most common in IDC. In addition, breast cancers resulting from the PTEN gene were more common in women (1009) than in men (12), with mortality occurring in 141 patients (140 women/one man). Moreover, despite a very powerful response to endocrine therapy (86.25%), Anti-HER2 therapy (38.4%) was more effective in pathological improvements.</p> Conclusion <p>Mutation, deletion and structural deteriorations cause breast cancer, is more common in women, entails a high mortality rate, and causes structural and cellular deteriorations and infiltration. Despite exhibiting a good response to endocrine therapy, responses are not high at the tissue level.</p>