To investigate whether combining both DNA methylation biomarkers and tumor markers could further improve the sensitivities for SP, AA, and CRC detection, the DNA methylation biomarker combination with the highest sensitivities, mSEPT9+mSDC2, was further combined with the four tumor marker combinations having similar performance, CEA alone, CEA+AFP, CEA+CA19-9, and CEA+AFP+CA19-9. Here, CEACAM5 is linked to neoplasm.