Introduction: The phosphatase and tensin homolog (PTEN) gene is localized on chromosome 10q23. It is a tumor suppressor gene that inhibits cell proliferation by regulating intracellular signaling pathways, and this activity can be abolished by mutations of the PTEN gene. PTEN is frequently mutated in a wide range of human tumors. Aim of the study: In this study, we evaluated the use of PTEN gene as a diagnostic marker to differentiate between endometrioid adenocarcinoma and premalignant lesions of the endometrium. Materials and methods: We used an immunohistochemical technique to evaluate the alteration of PTEN in 53 biopsy cases of normal, hyperplastic, and neoplastic endometrial tissue. Results: We found that PTEN expression was decreasing from hyperplasia (seven of 12 cases) to atypical hyperplasia (three of six cases), to endometrioid carcinoma (six of 21 cases), with statistically significant relationships. Conclusion: PTEN alteration of expression is one of the earliest changes in the process of endometrial tumorigenesis from hyperplasia to the carcinoma stage