Aim: The aim of this study was to evaluate the effectiveness of serum tissue polypeptide specific antigen (TPS) and aromatase activity in the detection of primary breast cancer and prediction of lymph node metastasis. Subjects and methods: Serum samples were obtained from 35 postmenopausal breast cancer females before surgery and 35 normal healthy volunteers. The clinicopathological  data of patients were obtained from their pathological reports. Determination of serum TPS was done using a ready-for-use ELISA kit. Serum total estradiol and total testosterone were determined using ready-for-use RIA kits and the ratio of estradiol to testosterone (E2/T) was used as an indirect expression of aromatase activity. Univariate and multivariate logistic regression analysis were performed to evaluate the association between these biomarkers and breast cancer, as well as lymph node metastasis. Results: For breast cancer prediction, either serum TPS or aromatase activity can be used with significant areas under the ROC curves of97% & 91.8%, respectively. For lymph node metastasis prediction, serum aromatase activity alone had the best predictive value, with a significant area under the ROC curve of 80.3%. Multivariate logistic regression analysis in which aromatase activity and TPS were included in one model gives 74% adequacy in prediction of lymph node metastasis. Conclusion:To predict breast cancer, either serum TPS or aromatase activity can be applied, while, for prediction of lymph node metastasis serum aromatase activity is recommended.