Over the past decade, studies on microRNA (miRNA) and cancer quickly became known. miRNAs are small non-coding RNAs that play a vital role in regulation of gene expression. In the present study, the expression of miR-27b, miR-29a, and miR-155, their prognostic roles, and their potential targets in chronic lymphocytic leukemia (CLL) and breast cancer (BC) by qRT-PCR were investigated. In two case-control studies, qRT-PCR was used to analyze the peripheral blood serum of 15 CLL patients and tissue samples of 15 BC patients for the expression of miR-27b, miR-29a, and miR-155. miRNA expression levels were calculated using the qRT-PCR method. The results revealed a significant increase in the expression of all miRNAs in patients with BC and CLL compared with respective healthy groups (p <0.001). In BC patients, there was a significant difference between the expression of miR-155 and miR-29a (p <0.05), miR-155 and miR-27b (p <0.01), and miR-27b and miR-29a (p <0.001). In CLL patients, a significant difference between expression of both miR-27b and miR-29a compared with expression of miR-155 (p <0.001) was found. Furthermore, a significant association between miR-155 and prevascular invasion was found. Significantly, elevated circulating miRNAs were shown to be BC specific and could differentiate BC tissues from the controls. It was demonstrated that miRNAs used in this study and their expression profiles can be developed as biomarkers for early diagnosis and prognosis of CLL and BC. Further studies utilizing a larger test group of patients would provide identification of miRNAs as key players in intercellular interactions.