The objective of the present study was to investigate a comparative estimation screening method of prostate specific antigen levels in serum samples with immunohistochemistry results for analysis expression of prostate specific antigen in female breast tissues at benign breast hyperplasia and breast cancer. This study was applied on 65 women suffering from breast cancer, 31 of them have benign breast hyperplasia and 34 have malignant breast cancer. Each group was divided into 2 subgroups, pre and postmenopause, both subgroups were compared with 15 normal cases to assess serum and tissue PSA in benign and malignant patients in pre and post menopause state by immunoradiometric assay in blood and immunohistochemistry in tissue. No significant difference in serum Total PSA concentration between any of the studied cases. However, there were different variations in the distribution of PSA in the breast tumor tissue, with complete absence of PSA in the tissue samples of the malignant in postmenopausal patients. In conclusion, PSA presence in benign breast hyperplasia in either serum or tissue may show clinical value regarding the diagnosis and prognosis of the disease.