To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer.A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis.First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival.Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.