Background: Early detection of breast cancer is paramount for accurate treatment and microRNAs represent the hopeful markers in cancer biology. Aims: To determine the differential co-expression and correlation of tissue and plasma exosomal miRNA-155 and miRNA-21 and their impact on the tissue inhibitor of metalloproteinase 3 (TIMP3) in fostering breast cancer metastasis. Materials and methods: MicroRNA-155 and miRNA-21 were extracted from plasma exosomal and tumor tissues of 60 women with breast tumors, and from plasma of 30 healthy women and miRNA expression was quantified by SYBR Green real-time polymerase chain reaction technique. The results were correlated with TIMP3 protein expression and patients’ clinico-pathological profiles. Results: The concomitant significant overexpression of plasma exosomal and tissue miRNA-21 and miRNA-155 was observed in invasive ductal carcinoma more than those of ductal carcinoma in situ and invasive lobular carcinoma. The miRNAs expression is also significantly associated with the advance of TNM staging and high tumor grade with positive correlation of circulating plasma exosomal miRNA with tissue miRNAs in the breast cancer group. The low TIMP3 expression was inversely associated with tissue and exosomal miRNAs expression. The area under curve, sensitivity, and specificity for miRNA-155 were 0.791, 73.3%, 80%, and for miRNA-21 were 0.925, 90%, and 86.7%, respectively. Conclusion: the positive interrelation of plasma exosomal miRNA-21 and 155 and their corresponding tissue miRNAs signifies role of cargos of these miRNAs in tumor metastasis and shed light on the invasive ability of cancer cells through activation of TIMP3/miRNA-21 expression.