Breast cancer (BC) is one of the most dangerous malignant diseases in females. However, the reliable serum biomarkers of BC still need to be explored. Chemerin levels have been found to be associated with different types of cancer. This study aimed to evaluate the role of serum chemerin as a biomarker of BC diagnosis, as well as the correlation between serum chemerin levels and clinicopathological features. The serum from 248 BC patients, 30 breast benign tumor patients, and 103 healthy controls were collected and serum chemerin levels were determined with enzyme-linked immunosorbent assay. We found that serum levels of chemerin in BC patients were higher than those in healthy control individuals (p < 0.05). The area under the ROC curve (AUC) for chemerin, CA15-3 and CEA was 0.703, 0.662 and 0.581, respectively, in distinguishing between breast cancer patients from healthy individuals, and the chemerin cutoff value was 100.327 ng/ml with a sensitivity of 56.60% and a specificity of 98.10%. The AUC for chemerin + CA15-3 was 0.822, which was higher than that for chemerin + CEA and CEA + CA15-3. Moreover, serum levels of chemerin were significantly associated with histologic grade, Ki67 expression, and menopausal status. However, no significant association was found between serum levels of chemerin and age, tumor size, metastase, ER status, PR status, and HER-2 status. Overall, our study suggested that the combination of chemerin with CA15-3 achieves relatively better diagnostic performance in the breast cancer. Elevated serum chemerin is associated with Ki67 expression levels and histologic grade.