Background: Breast cancer is the second leading cause of cancer death after lung cancer. Discovering molecular biomarkers is necessary for disease management that includes prognosis prediction and preventive treatment. The aim of this study is to evaluate the expression value of p53 and PTEN as molecular biomarkers of breast cancer and their relation with clinicopathological characteristics.Methods: In this study, 100 breast cancer and 20 normal samples were subjected to investigation. Total RNA was isolated and we measured RNA expression by realtime RT-PCR. Data were analyzed by REST 2009 and SPSS.Results: Gene expression results showed up-regulation of P53 in 53 breast cancer subjects and PTEN in 52 breast cancer subjects compared with normal controls. However, there was lower P53 expression in 25 breast cancer samples compared to normal tissues. PTEN expression was lower in 26 breast cancer samples than normal tissues. p53 showed a significant relationship to HER2 receptor (P=0.024) and menopausal status (P=0.013); no significant relationships existed with other clinicopathological parameters (P>0.05). PTEN had the only significant correlation with lymphatic invasion (P=0.046) without any relation with other clinicopathological features (P>0.05). PTEN expression had no significant association with p53 expression in the studied population (P=0.074).Conclusion: Combined detection of PTEN and p53 may have the potential to estimate the pathobiological behavior and prognosis of breast cancer. Due to the heterogeneous nature of cancer and the presence of different factors involved in the clinical situation of breast cancer, we suggest a study of a larger population and more biomarkers.