In this study, we evaluated a new blood‐based early CRC screening assay, ColoDefense test, which detects either of two methylation biomarkers, SEPT9 and SDC2. The results demonstrated that its detection rates for AA and CRC positive were significantly improved upon either methylated SEPT9 or methylated SDC2 alone without significant impact on specificity. This evidence concerns the gene SDC2 and colorectal carcinoma.