Objective: Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of breast cancer and the initiation of metastasis with poor prognosis leading to death. In this study we compared serum circulating micro RNA21 expression and its correlation to metastases in different stages of human breast cancer as a novel noninvasive biomarker that could be used for early detection. Methods: We analyzed the expression of miRNA-21 by quantitative real-time PCR, in 40 patients at different stages of breast cancer and compare its expression with another 20 healthy volunteers as control group. Results: miRNA-21 was significantly up-regulated in the early stage of breast cancer as compared to healthy control group (p 0.01). miRNA-21 was also higher expressed in patients with metastases as compared to healthy control group (p 0.01). There was positive correlation between miRNA-21 expression and the stage of the disease, and strong association between miR-21 over expression and the degree of invasiveness of the tumor. Conclusion: In the context of other studies that demonstrated the increased miRNA-21 expression in metastatic tumors, our results can mark miR-21 in different stages of breast cancer to be used as a potentially strong diagnostic and prognostic early biomarker and also these results raise the question whether or not miRNA-21 might be involved in the initiation of metastases.