Despite the improvement of programmatic screening, adjuvant chemotherapy, and curative resection, colon cancer, with increasing incidence and mortality rates, still poses a significant public health challenge as the third most commonly diagnosed and second most fatal cancer worldwide.1 The myriad of benefits, encompassing the improved survival rates, treatment outcomes, and cost efficiency, further underscore the criticality of early colon cancer diagnosis. Hence, there is a pressing need to identify more potent biomarkers for improving the accuracy of colon cancer diagnosis. In summary, we identified three methylation-related biomarkers that exhibit excellent diagnostic performance, suggesting their significant potential for its application as noninvasive clinical biomarkers in the diagnosis of colon cancer.