Breast cancer is a global public health burden. The stage at diagnosis is an important predictor of patient outcome. Thus there is an urgent need for developing more robust biomarkers. The discovery of circulating microRNAs along with their important role in cancer initiation and progression highlights their potential use as a non-invasive biomarker for cancer detection, evaluation, and follow-up. MicroRNA-21, in particular, has attracted a great deal of attention, since it is one of the most highly up-regulated microRNAs in many cancers. Herein, serum microRNA-21 levels were assessed in breast cancer patients, asymptomatic high-risk individuals and healthy individuals. In addition, expression levels of microRNA-21 in patients were re-evaluated after curative tumor resection. Current results could have crucial clinical applications in screening, diagnosis, and monitoring of this devastating disease.