The NCCN Guidelines recommend consideration of referral to a clinician with expertise in genetic testing for evaluation of constitutional MLH1 methylation testing in patients with early-onset CRC (≤55 years), no BRAF V600E PV, loss of MLH1 on IHC, and no MLH1 GPVs, or more than one tumor with MLH1 promoter hypermethylation at any age [59,88]. Here, MLH1 is linked to colorectal carcinoma.