Present management algorithms for patients with gastroesophageal reflux disease (GERD) limit endoscopy to patients with advanced disease. When endoscopy is performed, biopsy is limited to patients who have a visible columnar-lined esophagus. Biopsy is not recommended for patients whose endoscopy is normal. This algorithm results in the failure to evaluate patients with early stages of GERD at a pathologic level. We report 714 patients with normal endoscopic findings irrespective of symptoms who had adequate biopsies taken from the squamocolumnar junction and the area 1-cm distal to this from mucosa that had rugal folds. Concurrent biopsies were also taken from the gastric body and/or antrum. All patients had a gap between their esophageal squamous epithelium and gastric oxyntic mucosa in the junctional region composed of oxyntocardiac ± cardiac ± intestinal epithelia. A total of 643 (90.1%) patients had no significant pathology in the gastric antrum and/or body, indicating that the squamooxyntic gap was an isolated abnormality in this region in all but 71 (9.9%) patients. The gap contained only oxyntocardiac epithelium in 71 (9.9%) patients, cardiac mucosa without intestinal metaplasia in 482 (67.5%) patients, and intestinal metaplasia in 161 (22.6%) patients. The pathologic interpretation of biopsies taken from the gastroesophageal junction is confusing and has significant interobserver variation. This results from lack of agreement as to whether these biopsies originate in the proximal stomach ("gastric cardia") or in the esophagus. We provide evidence that the presence of oxyntocardiac ± cardiac ± intestinal epithelia in biopsies from patients who are endoscopically normal is diagnostic of a dilated GERD-damaged distal esophagus. The dilated distal esophagus is the pathologic manifestation of destruction of the abdominal segment of the lower esophageal sphincter. Its presence is the pathologic basis of early GERD, which is missed if patients who are endoscopically normal are not biopsied, as is the present recommendation. Its recognition allows for accurate and evidence-based interpretation of biopsies from this region and removes the present confusion and permits the development of a reproducible pathologic diagnostic method.