The biomarker significance of three chemokines (CXCL8, CXCL10 and CXCL16) was evaluated in sera of 45 breast cancer (BC) and 28 benign breast lesion (BBL) patients, as well as 20 control women. Clinical stage and tumor expression of estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor-2 (HER-2) receptors were considered in this evaluation. The results demonstrated that CXCL8, CXCL10 and CXCL16 showed a significant increased median in BC and BBL patients compared to control (CXCL8: 47.3 and 25.7 vs. 15.0; CXCL10: 37.6 and 30.7 vs. 13.1; CXCL16; 27.9 and 25.2 vs. 19.2 pg/ml, respectively). The increased levels of CXCL8 and CXCL16 were more pronounced in triple-negative and HER-2 positive patients, respectively. Binary logistic regression analysis revealed that CXCL8 was a significant predictor of BC, and such prediction was more depicted in triple-negative patients. The receiver operating characteristic analysis also revealed that CXCL8 recorded an area under curve of 0.998 in BC patients. In conclusion, CXCL8 is a potential biomarker for BC, especially when ER, PgR and HER-2 expression is considered. In this context, the predictive significance of CXCL8 in influencing BC progression is suggested in triple-negative patients.