Evidence that inherited susceptibility plays a role in the risk of malignancy comes from three separate sources. These observations are that: 1. In some syndromes which are rare in the general population but which are clearly genetically determined, there is a dramatically increased risk of cancer in gene carriers over and above that of the general population. Often these syndromes predispose to cancers which are rare outside this context and the cancers are diagnosed at atypically young ages. 2. Occasionally, families are found which contain a number of cases of ‘common’ cancers and the number of such cases in these families far exceeds that predicted by population rates. Again, many of these families exhibit cancers at noticeably young ages. 3. On a population level there is an increased risk of cancer to relatives of cancer cases; in many cases the relatives are at increased risk of the same cancer although relatives may also be at increased risk of other cancers.