Background. Breast cancer is the most common cancer and the leading cause of cancer death for women, a third of women are diagnosed with breast cancer at a late stage when the disease has a poor prognosis. Serum tumor markers have been widely used as noninvasive tools for measuring treatment response, early diagnosis of recurrence and predicting prognosis. In breast cancer, the most widely used serum tumor markers are cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA). The aim of this study was to investigate the association of serum CA15-3 and CEA levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). Patients and methods. This retrospective study was conducted on 50 patients who had used to predict response to chemotherapy in patients with metastatic breast cancer. The concentration of serum CA15-3 and CEA levels were measured using chemiluminescent enzyme immunoassays (ABBOTT ARCHITECT). The upper limits of normal for CA15-3 and CEA were 31.3 U/ml and 5 ng/ml, respectively. Result. Of the 50 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 37 (74%) and 32 (64%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P=0.005 and P=0.008, respectively). Elevated CA 15-3 level was correlated with bone metastasis (P=0.047). Conclusion. CA 15-3 and CEA level elevation at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtype; these serum tumor markers are frequently increased in the HER2-enriched and triple negative (TN) molecular subtypes of breast cancer.