In this study, the MSI-high tumors with PIK3CA exon 20 mutations were equally distributed between those resulting from MLH1 methylation (non-familial) and those likely to have resulted from a germline mismatch repair gene mutation (putative Lynch syndrome) suggesting no strong link between exon 20 mutations and either familial or non-familial MSI-high colorectal carcinomas, although the total number of tumors in this group was small (n = 8). This evidence concerns the gene PIK3CA and Lynch syndrome.