Colonocyte exfoliation in the human colon constitutes a unique mechanism of cell population control that can undergo significant changes under different physiological and pathological conditions. Being closely related to the apoptosis and anoikis, cell exfoliation from colonic epithelium appears to be a relatively rare event in normal conditions, but its rate dramatically increases in neoplasia, when cell removal by apoptosis in situ does not function properly. Several studies show that significant numbers of exfoliated colonocytes are not lost in the faecal contents of the gut, but retained in the mucocellular layer overlying colonic mucosa. Recent observations allow hypothesizing that the mucocellular layer containing exfoliated colonocytes may gradually migrate distally, eventually leading to the accumulation of the cells exfoliated from malignant colorectal tumours on the surface of the rectal mucosa. Implications of exfoliated colonocyte analysis to colorectal cancer screening and early diagnosis are discussed.