Our original ERC project shows that a biological system which corrects errors arising during DNA replication (DNA mismatch repair, MMR) plays a crucial role in cancer avoidance. We aim to conduct a proof of concept of the idea that functional assessment of MMR efficiency can be used to recognize individuals with decreased MMR capacity (i.e., Lynch syndrome). The projected outcome is a diagnostic kit that can be used by health care providers. Individuals whose test result indicates abnormality would be at notable risk to develop cancer. The traditional diagnostic workflow to identify MMR gene (Lynch syndrome) mutation carriers involves several phases (tumor studies, blood tests, in vitro tests for pathogenicity) and proceeds from detecting a defect, typically via biopsy of an already established tumor. In an important distinction, the present protocol consists of only one step, detection of decreased MMR capacity in a constitutional tissue, which can be followed by efforts to identify an underlying genetic or epigenetic defect if one so wishes (but not necessarily). Contrary to traditional tests, the present method allows for the recognition of individuals with increased cancer susceptibility due to deficient MMR even in cases where no family member has, yet, developed cancer, where mutation tests result in no detectable change, and where the underlying change is not genetic but epigenetic (regulatory).