Background: Tumor marker determinations are helpful parameters in the control and follow-up of the clinical course of neoplastic diseases. The serum concentrations of the three tumor markers CEA, CA 15-3 and MCA have been evaluated to comparatively investigate their clinical relevance in breast cancer patients. Patients and Methods: Simultaneous determinations of the serum concentrations of the three tumor markers CEA, CA 15-3 and MCA were performed in 419 sequential breast cancer patients. CEA and MCA were determined by means of enzyme immunoassays and CA 15-3 by a radio-immunoassay. Results: The serum concentrations of all three tumor markers correlate with tumor activity and tumor mass. The receiver operating characteristics (ROC) curves show that CA 15-3 has the greatest sensitivity and specificity. All three tumor markers did not reveal any dependence on age, but on the location of metastases; the median serum values decrease in the following sequence: osseous, visceral, and soft-tissue metastases. With a combination of tumor markers, the gain in sensitivity is associated with a loss of specificity, the combination of CEA + CA 15-3 appears to be the most favorable one. The combination of all three tumor markers does not show any advantage over the double combination CEA + CA 15-3. Conclusions: CA 15-3 has the highest sensitivity and specificity. As a combination of tumor markers CA 15-3 + CEA is recommended in breast cancer patients.