Circulating microRNAs (miRs) have attracted a great deal of attention as promising novel markers for various diseases. Our study aimed at evaluating the clinical utility of specific types of plasma miRs as diagnostic biomarkers in early-stage breast cancer (BC) patients and to study their relation with breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) mutations in BC patients and high-risk females. The study included 45 early-stage BC patients (30 non-familial and 15 familial), 15 high-risk subjects and 20 clinically healthy females as control. Using quantitative real-time polymerase chain reaction (RT-PCR), the relative expression levels of some plasma miRs (10b, 21, 155, 145 and let-7c) were determined in breast cancer patients and high-risk, compared to controls. Also, multiplex PCR was applied for the detection of 185delAG and 5382insC mutations in BRCA1 gene, and 6174delT mutation in BRCA2 gene using multiplex PCR and mutations were confirmed using High Resolution Melt (HRM) technique. Plasma miR-10b and miR-21 levels were significantly up-regulated, while miR-155 and miR-let-7c levels were significantly down-regulated in BC patients and high-risk subjects, compared to controls. MiR-21 was significantly up-regulated, whereas miR-155 level was significantly down-regulated in patients with lymphatic invasion. MiR-21 was showed a significant association with mutation in exon 2 of BRCA 1 in high-risk individuals. Deregulated expression of miR-10b, miR-21, miR-155, and let-7c serves as a potential non-invasive diagnostic marker in early-stage II BC, and surveillance biomarkers for individuals at a higher-expected risk of developing BC. Also, high-risk individuals harbor classical mutations in BRCA1 gene, considering it a high priority for these individuals to have a strict follow-up.