Previously a higher preoperative sensitivity of the mucin like glycoprotein Mammary Serum Antigen (MSA) compared to established tumor markers was reported. The aim of our study was the comparison of MSA and CA 549, CA 15-3 and CEA in primary breast cancer and the correlation to prognostic factors. In 119 patients MSA and CA 549 serum levels were analysed by ELISA, CEA and CA 15-3 levels by LIA. We received the following sensitivities: 30.2% for MSA (cut off = 55 U/mL), 21.8% for CA 549 (cut off = 12.6 U/mL), 20.5% for CA 15-3 (cut off = 25 U/ml) and 10.7% for CEA (cut off = 6 ng/ml). Significant correlations were found between MSA concentrations and grading (p = 0.006), tumor size (p = 0.005) and metastases (p = 0.03). No correlations were found to tumor type, hormone receptors, lymph node status and cathepsin D. MSA is a valuable tumor marker with the highest preoperative sensitivity. Further studies on the value of MSA in the follow-up are necessary.