BACKGROUND: MicroRNAs (miRNAs), small RNA molecules of approximately 22 nucleotides, have been shown to be up- or downregulated in specific cell types and disease states. These molecules have become recognized as one of the major regulatory gatekeepers of coding genes in the human genome. CONTENT: We review the structure, nomenclature, mechanism of action, technologies used for miRNA detection, and associations of iniRNAs with human cancer. miRNAs are produced in a tissue-specific manner, and changes in miRNA within a tissue type can be correlated with disease status. iniRNAs appear to regulate mRNA translation and degradation via mechanisms that are dependent on the degree of complementarity between the miRNA and rnRNA molecules. miRNAs can be detected via several methods, such as microarrays, bead-based arrays, and quantitative real-time PCR. The tissue concentrations of specific miRNAs have been associated with tumor invasiveness, metastatic potential, and other clinical characteristics for several types of cancers, including chronic lymphocytic leukemia, and breast, colorectal, hepatic, lung, pancreatic, and prostate cancers. SUMMARY: By targeting and controlling the expression of mRNA, miRNAs can control highly complex signal-transduction pathways and other biological pathways. The biologic roles of miRNAs in cancer suggest a correlation with prognosis and therapeutic outcome. Further investigation of these roles may lead to new approaches for the categorization, diagnosis, and treatment of human cancers. (C) 2009 American Association for Clinical Chemistry