Transition zones (TZs) are regions in the body where two different types of epithelial tissue meet resulting in the appearance of a distinct abrupt transition. These TZs are found in numerous locations within the body, including the cornea-conjunctiva junction, esophagogastric junction, gastro-duodenal junction, endo-ectocervix junction, ileocecal junction, and anorectal junction. Several of these TZs are often associated with the development of cancer, in some cases due to viral transformation by the human papilloma virus (HPV). The underlying molecular and cellular basis for this tumor susceptibiblity is unknown. The distinct epithelial morphology and location results in unique properties being conferred upon this epithelial tissue, as different signaling cues and cell surface markers are apparent. Importantly, the natural state of TZs closely resembles that of a pre-lesional epithelium, as several proteins that are induced during wounding are expressed specifically within this region, which may contribute to transformation. This region may also act as a stem cell niche, and as such, represents a key location for cellular transformation by accumulated genetic mutations or viral transformation resulting in tumor formation.