During the past few years there has been great interest in the development of circulating microRNAs (miRNAs) as stable blood-based biomarkers for cancer detection. Deregulation of miRNAs in blood samples has shown considerable clinical utilities in cancers. Due to poorly characterized preanalytical and analytical variables and the lack of a standardized measurement protocol, the application of these miRNA fingerprints is hindered by conflicting results. In this review,we outline our current understanding of preanalytically and analytically confounding factors. We believe that great consideration should be taken in the development of circulating miRNA as tumor biomarkers.