According to the definition delivred by the WHO, a
biomarker, independently from its role that may be indicative of exposure, response or effect, is inevitably linked to a clinical outcome or to a disease. The presence of a continuum from early
biological events to
therapy, and prognosis is the unifying mechanism that justifies this conclusion. Traditionally, the technical and inter-individual variability of the assays, together with the long duration between early pathogenetic events and the disease, prevented clinical applications to these
biomarkers. These limitations became less important with the emerging of personalized preventive medicine because of the focus on disease prediction and prevention, and the recommended use of all data concerning measurable patient's features. Several papers have been published on the best validation procedures for translating
biomarkers to real life. The history of
cholesterol concentration is extensively discussed as a reliable example of a
biomarker that - after a long and controversial validation process - is currently used in clinical practice. The frequency of micronucleated cells is a reliable
biomarker for the pathogenesis of
cancer and other
non-communicable diseases, and the link with clinical outcomes is substantiated by epidemiological evidence and strong mechanistic basis. Available literature concerning the use of the micronucleus assay in clinical studies is discussed, and a suitable three-levels road-map driving this
biomarker towards clinical practice is presented. Under the perspective of
personalized medicine, the use of the micronucleus assays can play a decisive role in addressing preventive and therapeutic strategies of
chronic diseases. In many cases the MN assay is either currently used in clinical practice or classified as adequate to consider translation into practice. The roadmap to clinical validation of the micronucleus assay finds inspiration from the history of
biomarkers such as
cholesterol, which clearly showed that the evidence from prospective studies or RCTs is critical to achieve the required level of trust from the healthcare profession. (307 words).