Objective:To investigate the expression of soluble B7-H4 molecules (soluble B7-H4, sB7-H4) in serum of patients with breast cancer and its clinical signiifcance. Methods:Seventy patients with breast cancer, 41 patients with benign breast disease and 28 healthy females were respectively selected as breast cancer group, benign control group and healthy control group. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the content of serum sB7-H4 in three groups, and the clinical correlation with content of serum sB7-H4 in patients with breast cancer was analyzed. Besides, the expression of B7-H4 mRNA and proteins in breast cancer tissue and normal tissue adjacent to cancer was detected respectively with polymerase chain reaction (PCR) and immunohistochemical method. Results:The content of serum sB7-H4 in breast cancer group was obviously higher than in benign control group (U = 844.0, P < 0.01) and healthy control group (U = 727.0, P < 0.05). The content of sB7-H4 in serum of patients with breast cancer was signiifcantly associated with lymph node metastasis (χ2 = 6.944, P < 0.01), not with other clinical pathological parameters. The expression of B7-H4 mRNA and proteins was detectable in breast cancer tissue and normal tissue adjacent to cancer. Conclusion:In serum of patients with breast cancer, the content of sB7-H4 is increased notably and related to lymph node metastasis, hence it can be considered as a potential serum marker in the diagnosis and treatment of breast cancer.