Germline mutations in the human checkpoint gene, hCHK2, were first identified in 1999 in cases of Li-Fraumeni syndrome. Recent studies have demonstrated that the hCHK2 1100delC mutation acts as a low-penetrance tumour suppressor gene in familial breast cancer not associated with mutations in BRCA1 or BRCA2. The present article describes the published studies on hCHK2 1100delC and addresses some of the key questions raised.