Abstract: Objective To investigate the serum soluble B7-H4（sB7-H4）level in breast cancer patients and its clinical implications. Methods The sB7-H4 levels in sera from 70 cases of breast cancer patients，41 cases of benign breast disease patients and 28 cases of healthy female donors were detected by ELISA. Clinical implications were also analyzed.B7-H4 mRNA and protein expression in both breast cancer and adjacent normal tissues was detected by PCR and immunohistochemistry methods，respectively.Results The median sB7-H4 level in sera of breast cancer patients was 26.54μg/ml,significantly higher than 5.69μg/ml of benign breast disease patients（U=844.0，P＜0.01）, as well as 15.71μg/ml in healthy donors （U=727.0，P＜0.05）. The sB7-H4 level in sera from breast cancer patients was positively correlated to lymph nodal metastasis status（χ2=6.944，P＜0.01），while it was not correlated to any other clinicopathological parameters. We also verified that both mRNA and protein expression of B7-H4 could be detected in breast cancer tissues as well as adjacent normal tissues，respectively. Conclusion The increased sB7-H4 level in sera from breast cancer patients is significantly correlated to nodal metastasis status，which suggests that the sB7-H4 level may be developed as a candidate serum marker for breast cancer diagnosis.