In summary, this systematic review and meta-analysis yield some conclusions: the MLH1 methylation in total CRC was 20.3%; they were 18.7% in sporadic CRC and 16.4% in LS CRC, respectively; MLH1 promoter methylation may be significantly associated with gender, tumor location, tumor differentiation, MSI, MLH1 protein expression, and BRAF mutation. The gene discussed is BRAF; the disease is Leigh syndrome.