Background: Cancer antigen 15-3 and carcinoembryonic antigen are used in clinical and laboratory diagnosis of metastatic breast cancer. Previous studies have noted conflicting results about the association between carcinoembryonic antigen and cancer antigen 15-3 in metastatic breast cancer. The present study examined serum tumor marker levels of carcinoembryonic antigen and cancer antigen 15-3 among patients with different subtypes of metastatic breast cancer.Methods: In this cross-sectional study, we assessed metastatic breast cancer patients diagnosed between 2005 and 2012 who referred to academic Hospitals affiliated with Mashhad University of Medical Sciences. The patients were selected by systematic randomization sampling. Demographic, clinical, pathological, and therapeutic data were collected from patients’ hospital records. Statistical analyses were performed by Statistical Package for the Social Sciences version 16.0 software.Results: A total of 298 eligible patients enrolled in the study. Patients’ median age was 48.39±12.57 years. Elevated serum levels of carcinoembryonic antigen were identified in 65.17% of patients and cancer antigen 15-3 in 57.29% of patients. Based on molecular subtype categorization, 109 (39.5%) patients were human epidermal growth factor receptor 2 negative and 105 (38.0%) patients were in the luminal group. There was no significant correlation between serum carcinoembryonic antigen and cancer antigen 15-3 with subtypes of the tumor. The most common sites for metastasis were bones and liver, respectively. However, there was no significant correlation between serum carcinoembryonic antigen and cancer antigen 15-3 with the site of metastasis. There was a significant association between serum carcinoembryonic antigen level and stages IIA and IV.Conclusion: One of the most significant findings of the current study was the increased serum carcinoembryonic antigen and cancer antigen 15-3 levels in most metastatic breast cancer participants. We postulate that regular measurement of serum cancer antigen 15-3 and carcinoembryonic antigen could be useful for earlier detection and prediction of outcomes.