If IHC screening reveals a loss of expression of one or more MMR proteins and if gene methylation can be excluded (MLH1 promoter), tumor sequencing may uncover the underlying pathogenic variants and germ line testing will reveal whether there is a hereditary predisposition in LS patients [39,100,101,102,104,105,106,107,108,109,110]. The gene discussed is MLH1; the disease is neoplasm.