Screening for colon cancer (CC) allows for diagnosis of the early stage for malignancy and potentially reduces disease mortality as the cancer could be cured at disease earliest stages. Early detection could be desirable if accurate, practical and cost effective diagnostic measures for this cancer are available. Mortality and morbidity from colon cancer represent a major health problem involving a malignant disease that is theoretically preventable through screening. Current screening methods (e.g., the immunological fecal occult blood test, FOBTi, obtained from patients' medical records) either lacks sensitivity and requires dietary restriction, which impedes compliance and use; are costly (e.g., colonoscopy), which decreases compliance; or could lead to mortality. In comparison to the FOBT test, a noninvasive sensitive screen for which there is no requirement for dietary restriction would be a more convenient test. Colorectal cancer (CRC) is the only cancer for which screening by colonoscopy is recommended. Although colonoscopy is a reliable screening tool, its invasive nature, accompanying abdominal pain, potential complications and high cost have hampered the application of this screening method worldwide.A novel screening approach using the stable miRNA molecules, which are relatively nondegradable when extracted from noninvasive stool and semi-invasive blood samples by currently available commercial kits and manipulated thereafter, would be preferable to a transcriptomic messenger (m)RNA-, a mutation DNA-, an epigenetic-or a proteomic-based test. The approach utilizes reverse transcriptase (RT), followed by a modified quantitative real-time polymerase chain reaction (qPCR). Although exosomal RNA would not be measured, using a restricted extraction of total RNA from stool or blood, then a parallel test could also be carried out on RNA obtained from stool or plasma samples, and appropriate corrections for exsosomal loss can be made to obtain accurate and quantitative results. Eventually, a chip would be developed to facilitate diagnosis, as has been carried out for the quantification of genetically modified organisms (GMOs) in foods. The gold standard to which the molecular miRNA test is compared is colonoscopy. If performance criteria are met, as detailed herein, then a miRNA test in human stool or blood samples based on high throughput automated technologies and quantitative expression measurements --commonly used in the diagnostic clinical laboratory--would eventually be advanced to the clinical setting, which will make a vivid impact on the prevention of colon cancer.Correspondence to: Farid E. Ahmed, GEM