The ONCOSCREEN project aims to overcome the shortcomings of current colorectal cancer (CRC) screening methods by developing a European colorectal cancer “shield” based on novel, more accurate, and affordable risk-based screening methods. These innovations will be clinically validated in a multicentre observational study involving 4100 European citizens and patients from 10 countries. It will also provide tools and methods for risk-based early detection for citizens, an integrated diagnostic decision support tool for clinicians, and intelligent surveillance tools for policy makers.