MSH6 germline mutations have been mostly observed in atypical HNPCC families presenting a weaker family history, possibly caused by lower penetrance of mutations in this gene (Hendriks et al, 2004; Plaschke et al, 2004), and tumours in these families may be ‘microsatellite stable’, may present ‘low-frequency microsatellite instability’ (MSI-L), or may be MSI-H (Wu et al, 1999; Plaschke et al, 2000; Berends et al, 2002). This evidence concerns the gene MSH6 and neoplasm.