Mammary serum antigen (MSA) serum levels were evaluated for its association with histopathologic outcome of breast biopsies. 212 women were undergoing a diagnostic extirpation for suspicious lesions of the breast. Invasive breast cancer was found in 24.5%, in-situ-carcinomas in 7.1% respectively. 56.1% of the women were diagnosed with proliferating benign breast diseases and normal breast tissue was found in 12.3% of the patients. In all women pretherapeutic MSA-serum levels were measured by Inhibition-ELISA using the monoclonal antibody 3E1.2. The positivity-rates of MSA, CA15-3, TPA and CEA were compared separately and in combination. MSA was positive in 25% of breast cancer patients when a cut-off level of 55 U/ml was applied. The addition of CA15-3, TPA or CEA increased the sensitivity to 42.3% and the increment of the positivity-rate was smaller by addition of CA15-3, when compared with TPA or CEA. The highest MSA serum levels and positivity-rates were associated with malignant tumours, but there was no significant difference compared with benign epithelial proliferations (19.5% positivity rate). The lowest positivity-rate was detected in mesenchymal proliferations of the breast (4.8%, p = 0.02). To sum up one can say that MSA serum levels do not allow to discriminate benign from malignant breast diseases and MSA is 2.5 to 3 times more sensitive for the prediction of early stages breast cancer compared to CA15-3, TPA and CEA.