It is the epithelium of the colon which is perhaps most important to the understanding of colon cancer, for it is here where the vast majority of colon cancers begin. Colon epithelium has a flat appearing surface, but it is glandular tissue, primarily, and is characterized anatomically by long, thin microscopic pits known as crypts. (They are sometimes also called the glands of Lieberkuhn after the eighteenth century German anatomist who first described them.) These crypts measure about half a centimeter in depth. They contain three types of cells, known as the columnar absorptive cell, mucous-secreting goblet cells, and enteroendocrine cells.

There is an amazing turnover of epithelial cells, with the columnar absorptive and goblet cells having a lifetime of only a few days. These cells begin as undifferentiated (meaning without any recognizable distinguishing characteristics) cells in the deeper zones of the crypts and they move up to the surface where they take on their recognizable features. When cells reach the flat surface of the epithelium they begin to degenerate and eventually slough off into the lumen and become part of waste eliminated. The life cycle of a cell in this process is four to six days. The enteroendocrine cells probably survive a little longer than their columnar absorptive and goblet cell counterparts and probably migrate up the crypt (independently of them) as well. The epithelium lining the colon is thus replaced completely every four to six days and because of the constant renewal process that goes on in the bowel, the epithelium is particularly sensitive to noxious substances. [It is because of this constant turnover and sensitivity in the gastrointestinal tract that nausea, vomiting and diarrhea are common features of chemotherapy drug and radiation therapy toxicity.