Objective: The aim of this study was to explore the correlation of pretreatment serum tissue polypeptide specific antigen (TPS) with prognosis in primary breast cancer. Methods: A total of 361 patients with grades Ⅰ-Ⅲ breast cancer had been followed up from January 2001 to February 2011. Serumal TPS level was measured by enzyme-linked immunosorbent assays (ELISA). Univariate and multivariate analyses were used to investigate associations between pretreatment TPS level and clinicopathological parameters and patient outcomes. Results: First, at the univariate analysis, the expression of TPS was related with some clinicopathological traditional prognostic factors such as tumor size (P = 0.030), histologic grade (P = 0.001) and lymph node status (P = 0.008). Second, overall survival were significantly shorter among patients with elevated pretreatment serum TPS (P = 0.038). However, finally, multivariate Cox regression indicated that the level of pretreatment serum TPS was not an independent prognostic parameter for overall survival in primarily breast cancer patients (P > 0.05). Conclusion: The expression of pretreatment serum TPS is closely correlated with clinicopathology parameters and overall survival of patients with primarily breast cancer, but its level has no independent prognostic value.