Abstract. Serum biomarkers are of diagnostic value and can be used for follow-up and prognostic factors. However, serum protein biomarkers show limited diagnostic sensitivity and specificity in stand-alone assays breast cancer because their levels refect tumor burden. In this study, we reviewed the levels of CA15-3, TSGF, CA125 and CEA both in nipple discharge and serum in 179 cases of breast lesions to assess the clinical value of nipple discharge and serum tumor markers in diagnosis, follow-up and prognostic in breast cancer. Our results indicate that the nipple discharge and serum levels of CA15-3, TSGF, CA125 and CEA in breast carcinomas patients were significantly higher than those in the benign disease (P<0.01). Aditionally, The levels of the four tumor markers in nipple discharge were significantly higher than in the serum (P<0.01). The levels of the four biomarkers in nipple discharge had positive correlation with histological grade, clinical stage, the Ki-67 index, expression of VEGF and HER-2/neu, lymphnode metastas and tumor recurrence (P<0.05, respectively), and negative correlation with the level of ER or PR (P<0.05, respectively). The sensitivity of the four serum tumor markes in combination was only 69.77%, in contrast, the combined detection both in discharge and serum was 97.67%, and the negative predictive value was 99.03%. The sensitivity of combined detection both in nipple discharge and serum were significantly higher than other detection (P<0.05). The four tumor markers in nipple discharge are as novel biomarker in dignosis and judging the prognosis of breast cancer. The dynamic combined detection of the four tumor markers both in nipple discharge and serum are helpful to the stratification of preoperative patients and benefit to better prewarning markers for monitoring their recurrence and metastasis of tumors in clinic, but cannot increase the sensitivity of judging the patients with early breast cancer.