Hereditary non-polyposis colorectal cancer is an autosomal dominant inherited disorder that predisposes its carriers to an almost 100% lifetime risk of cancer, in particular colorectal and endometrial cancer. Germline mutations, resulting in a deficient DNA mismatch repair system, are responsible for the disease. Because of the lack of specific phenotypical features, clinical diagnosis in an individual patient is impossible and relies heavily on family history. Genetic diagnosis by mismatch detection is now possible in a substantial proportion of families. Thus there is a great need for reliable but simple criteria that will help clinicians to recognize patients and families who can be referred for genetic diagnostics. In this article the different criteria that have been formulated and published in recent years are reviewed and the results, in terms of the proportions of subjects satisfying the criteria who were found to have a germline mutation, are discussed. In most studies the criteria were evaluated in only a small number of subjects. A population-based study is currently being carried out in the north of The Netherlands that aims to include 400 patients fulfilling one of a few simple criteria. Mutation analysis will be performed in all patients. The results of this study will help in the formulation of accurate and simple criteria for use in clinical practice.