Abstract: Objective To detect the expression of a new tumor suppressor gene PTEN and DNA direct repair enzyme MGMT in gynecomastia. Methods Immunohistochemical SP method was used to detect expression of PTEN and MGMT protein in 68 cases of gynecomastia（experiment group） and 24 cases of mammary gland of normal man tissues（control group）. The selected examples were divided into three different age groups and three different histological types. Results The PTEN and MGMT protein were all expressed in nuclear of ductal cellula epithelialis. The expression level of PTEN and MGMT protein in gynecomastia was significantly lower than mammary gland of normal man tissues（P＜0.01）. There was difference between the expression of PTEN and MGMT protein in different age groups（P＜0.05）, moreover, the expression level of PTEN protein degraded in middle-aged group, older age-group, and young group by turns；the expression level of MGMT protein degraded in older age-group, middle-aged group, and young group by turns. The expression of PTEN and MGMT protein in three different histological types was different（P＜0.05）, and the expression level of them degraded in constrictive type, transitional type, and prosperous and intense type by turns. Conclusion This study suggests that the abnormal expression of tumor suppressor gene PTEN and MGMT in gynecomastia probably plays an important role in the development of gynecomastia.