Breast cancer represents a heterogeneous categorization of diseases which is on the increase in Basra/Iraq. Cancer antigen 15-3 (CA15-3) is frequently used tumor biomarker (TM) in metastatic breast cancer but may not be elevated. Conventional, diagnosis of breast cancer is achieved by clinical examination and histopathological confirmation. Therefore this study aim to estimate the role of CA -15-3 in diagnosis and confirming the diagnosis breast cancer. Present study included (51) women diagnosed with breast cancer. In study population age ranged from (30-70 years) old. The control group has consisted of (32) healthy women. Enzyme Linked Immunosorbent Assay (ELISA) was once used to measure Serum CA 15-3, p53. The study referred a raised amount of (CA15-3) in breast cancer patients (82.14±66.22) in comparison to healthy control group (8.72±2.06). Conversely, the data of this study were illustrated opposite result that there is a significance decrease P53 level in serum (P<0.01) in BC patients in comparison to healthy group. The current study appeared that there is a high significant increase (P value < 0.001) in CA 15- 3 levels in BC patients at stage III in comparison to coming primary stages; while P53 has decreased in the progressive stages. Regarding BC of patients. While there was no significant difference in the levels of biomarkers despite the progression of the grads of the disease. That there is an increase in the biomarker (CA15.3) in women with breast cancer, while there is a decrease in P53 in breast cancer patients, may be helpful as prognosis in diagnosis of breast cancer patients.