OBJECTIVE To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases. METHODS Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects. RESULTS The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05). CONCLUSIONS Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.