This study aimed to examine the cost-effectiveness of fecal biomarker M3 panel compared to fecal immunochemical test (FIT) and colonoscopy in an Asian population. In a hypothetical population of 100,000 persons aged 50 years who received FIT yearly, M3 biomarker yearly, or colonoscopy every 10 years until the age of 75 years. Participants with positive FOBT or a result of “high risk” identified using the M3 biomarker are offered colonoscopy. We assumed surveillance colonoscopy is repeated every 3 years, and examined the treatment cost. A comparison of various outcome measures was conducted using Markov modelling. The incremental cost-effectiveness ratio (ICER) of FIT, M3 biomarker, and colonoscopy was USD108,176, USD133,485 and USD159,596, respectively. Comparing with FIT, the use of M3 biomarker could lead to significantly smaller total loss of cancer-related life-years (2783 vs. 5279); a higher number of CRC cases prevented (1622 vs. 146), a higher proportion of CRC cases prevented (50.2% vs. 4.5%), more life-years saved (2852 vs. 339), and cheaper total costs per life-year saved (USD212,553 vs. 773,894). The total costs per life-year saved is more affordable than that achieved by colonoscopy as a primary screening tool (USD212,553 vs. USD236,909). The findings show that M3 biomarkers may be more cost-effective than colonoscopy.