Introduction MicroRNAs (miRNAs) are small, non-coding RNA segments that regulate gene expression via post-transcriptional inhibition and have roles in cell differentiation, proliferation, and apoptosis. Expression differs between tumor and normal tissue in several malignancies. Most work has focused on tissue and cell expression with few reports of circulating miRNAs in colorectal cancer. Available biomarkers for colorectal cancer have limited sensitivity and specificity, thus there is a need for new markers. Aims This study aimed to identify miRNAs that are differentially expressed in the blood of colorectal cancer patients compared to controls and to establish if this is specific to colorectal cancer and thus could be utilized as potential tumor markers. Methods Blood samples were collected from 63 colorectal cancer patients and 45 controls. Expression of 7 target miRNAs (miR-143, miR-145, miR-21, miR-30a-3p, miR-31, miR-34a, and miR-92) was measured using RQ-PCR. Results were correlated with clinicopathological data and analyzed. Analysis of differentially expressed circulating miRNAs was expanded to include 62 patients with prostate, renal, breast, and melanoma cancers. Results Analysis of the relative quantification of the target miRNAs showed significantly reduced expression (P?=?0.004) of miR-34a in colorectal cancer. MiR-34a was also significantly reduced in breast cancer (P?=?0.019). Conclusion This study demonstrates significantly reduced expression of circulating miR-34a in colorectal and breast cancer. This may have future application as part of a biomarker profile. J. Surg. Oncol. 2012; 106: 947952. (c) 2012 Wiley Periodicals, Inc.