Abstract - Background: Breast cancer is the most common malignancy with a high mortality in females worldwide. Tumor suppressor genes had significant role to maintain genome integrity and the cell cycle. In particular PTEN is a candidate tumor suppressor gene, It has a negative regulator of PI3K/AKT signaling pathway which has a major role in carcinogenesis and dysregulation of it occurs repeatedly in breast cancer. Aim: this article aimed to appraise the associations between PTEN expression in patient had breast cancer with clinic pathological parameters including: age, histological types, and status of estrogen receptor, progesterone receptor, and HER-2/nue receptor, to check the impact of its expression on clinical outcome. Materials and methods: in this case-control study, formalin fixed paraffin embedded tissue from sixty patients with breast carcinoma and twenty patients without cancer (as control groups). Labeled Streptavidin -Biotin (LSAB+ ) method used to detect PTEN protein expression, HER2/neu, ER and PR receptors by immunohistochemical assay, and then we correlate PTEN expression with each biomarkers and clinic pathological characteristics. Results: 29/60 (45.3%) of cases decreased PTEN expression while its expression retained in 31/60 (51%) of cases. Loss of expression significantly associated: with lymph node metastasis ( p-value=0.0008 ), high grade (p< 0.05 ) , high stage (p-value=0.0001 ) and with triple negative breast cancer (pvalue=0.03) . However, loss of PTEN protein expression did not correlate with age, histological types, estrogen, progesterone and HER-2 receptors status. Conclusion: PTEN loss can predict aggressive behavior and worse outcome in patients had breast cancer.