A novel pathophysiology of Barrett's esophagus and a new method of assessing biopsy specimens in patients with gastroesophageal reflux disease (GERD) are presented. This is based on the observation in autopsy studies of patients without GERD that the squamous epithelium of the esophagus transitions directly to fundic mucosa in many people and that the cardiac mucosa is of very short length in others. Available evidence suggests that what is termed gastric cardiac mucosa is in reality an abnormal mucosa resulting from metaplasia of the squamous epithelium of the esophagus as a result of GERD. The severity of GERD correlates with the length of metaplastic cardiac mucosa and further changes occurring in it, permitting development of a system that provides good correlation between biopsy histology and severity of GERD. Intestinal metaplasia ("Barrett's esophagus") always occurs in this metaplastic cardiac mucosa. The recognition of this new pathophysiology of Barrett's esophagus permits identification of the entire sequence whereby GERD leads to adenocarcinoma: GERD-->cardiac metaplasia of squamous epithelium-->reflux carditis-->intestinal metaplasia-->dysplasia-->adenocarcinoma. This article also attempts to develop a terminology that avoids use of the confusing term "Barrett's esophagus," which should be discarded.