Purpose: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the most frequently mutated human tumor suppressor genes. The present study aims at investigating role of PTEN mutation in breast carcinogenesis by analyzing PTEN mutation spectrum and PTEN protein expression in selected benign breast lesions versus breast cancer as regards comparison between PTEN immunohistochem-ical expression and PTEN mutations in studied cases. Patients and Methods: Fifty cases of breast lesions including 30 non-consecutive retrospective selected breast carcinoma (10 cases in-traductal breast carcinoma (DCIS). 20 cases of invasive breast ductal carcinoma) and 20 cases of benign proliferative breast lesions (10 fibro-adenoma, 10 fibrocystic disease). 10 cases ofnon- neoplastic breast tissue adjacent to selected lesions were taken as control. Cases were collected in the period 2004-2010, selected from files of pathology department, faculty of medicine- Benha University and Egyptian national cancer institute (NCI). Results: highly significant inverse correlation between PTEN immuno/expression and types of the disease (P