Somatic CTNNB1 mutations have been previously associated with MLH1 germline variants, and a rather low prevalence of CTNNB1-mutant tumors among MLH1-associated incident cancers compared to their reported frequency in MLH1-associated prevalent cancers is unexpected and could point at different routes of progression between MLH1-associated incident and prevalent cancers. The gene discussed is CTNNB1; the disease is cancer.