Background Breast cancer (BC) is the leading cause of cancer death in women worldwide. Most BC studies on candidate microRNAs were tissue specimen based. Recently, there has been a focus on the study of cell‐free circulating miRNAs as promising biomarkers in (BC) diagnosis and prognosis. Therefore, we aimed to investigate the circulating levels of miR‐10b and its target soluble E‐ cadherin as potentially easily accessible biomarkers for breast cancer. Methods Sixty‐one breast cancer patients and forty‐eight age‐ and sex‐matched healthy volunteers serving as a control group were enrolled in the present study. Serum samples were used to assess miRNA10b expression by TaqMan miRNA assay technique. In addition, soluble E‐cadherin expression level in serum was determined using ELISA technique. Result Circulating miR‐10b expression level and serum sE‐cadherin was significantly upregulated in patients with BC compared to controls. Moreover, serum miR‐10b displayed progressive up‐regulation in advanced stages with higher level in metastatic compared to non‐metastatic BC. Additionally, the combined use of both serum miR‐10b and sE‐cadherin revealed the highest sensitivity and specificity for detection of BC metastasis (92.9% and 97.9% respectively) with an area under curve (AUC) of 0.98, 95% CI (0.958–1.00). Conclusion Our data suggest that circulating miR‐10b could be utilized as a potential non‐invasive serum biomarker for diagnosis and prognosis of breast cancer with better performance to predict BC metastasis achieved on measuring it simultaneously with serum sE‐cadherin. Further studies with a large cohort of patients are warranted to validate the serum biomarker for breast cancer management.