Human DNA fragments, as well a as whole colonocytes, can be found in stool and interrogated for mutations associated with carcinogenesis. Multiplexed panels of point mutations in fecal DNA improved the sensitivity of cancer detection (51.6%; 95% CI, 34.8%-68%) compared with fecal occult blood testing (12.9%; 95% CI, 5.1-28.9). However, the multiplex panels are not more sensitive than fecal occult blood testing in detecting advanced adenomas. Markers of epigenetic events, such as DNA methylation of gene promoters in genes not previously known to be associated with carcinogenesis or colorectal cancer, have recently been shown to be potential markers for early detection. Future approaches to improve sensitivity of fecal DNA detection of colorectal adenocarcinoma may require the inclusion of epigenetic biomarkers, the use of colonocytes isolated from feces, or both.