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BRAFand MLH1promoter methylation testings have been proven effective prescreens for Lynch Syndrome. We aimed to compare different screening strategies for Lynch Syndrome in patients with MLH1(−) CRC. Patients with MLH1(−) CRC who had been tested for BRAFmutation and germline variants of DNA mismatch repair genes were included. We compared the sensitivities and specificities for identifying Lynch Syndrome and the cost-effectiveness of four screening approaches that used the following tests as prescreens: BRAFtesting, MLH1methylation testing, MLH1methylation & BRAFtesting, and MLH1methylation testing & Revised Bethesda Criteria. Of 109 patients included, 23 (21.1%) were Lynch Syndrome patients. BRAFmutation and MLH1methylation occurred in 6 (5.5%) and 40 (36.7%) patients, respectively. The sensitivity for identifying Lynch syndrome of BRAFtesting was 100%, but the specificity was only 7%. MLH1methylation testing had a lower sensitivity than BRAFtesting (97.5% vs 100%), but had a markedly higher specificity (45.3% vs 7%). The combination of the two testings had a slightly higher specificity than MLH1methylation testing alone (47.7% vs 45.3%). The MLH1methylation testing approach had a 10% lower cost of identifying MLH1(−) Lynch syndrome carriers per case than universal genetic testing, but it missed 4.5% of patients. BRAFand MLH1promoter methylation testings as prescreens for Lynch syndrome are less effective in Chinese patients with MLH1(−) CRC than in their Western counterparts. Universal genetic testing could be considered an up-front option for this population.