The microsatellite instability phenotype (MSI⁺) is observed in approximately 25% of colon cancers and 2% of rectal cancers. MSI⁺ is a hallmark of almost all hereditary non-polyposis colorectal cancers (HNPCC) where it is associated with germline mutations in one of the DNA mismatch repair genes.¹ However, the large majority of MSI⁺ cancers occur as sporadic cases that arise following methylation induced silencing of the hMLH1 gene promoter. Sporadic MSI⁺ tumours are believed to originate in serrated polyps and display frequent and concurrent methylation of gene promoter regions but low frequencies of KRAS and TP53 mutations.² In contrast, HNPCC associated MSI⁺ tumours originate in conventional adenomas and show frequent APC and KRAS mutations but infrequent methylation. Another striking difference is that BRAF mutations occur in most …