Between January and June 1998, all the outpatients attending the GI units of 2 tertiary centers in Lombardy (northern Italy) for upper GI tract endoscopy because of dyspeptic symptoms (chronic or recurrent pain or discomfort centered in the upper area of the abdomen) were prospectively studied. Excluded were patients younger than 12 years; those undergoing clinical workup for an upper GI tract disease suggested by previous radiographic or ultrasonographic findings; those referred for malabsorption, suspected celiac disease, or iron deficiency anemia; those receiving regular follow-up for a known disease (eg, peptic ulcer); and those with classic heartburn or acid regurgitation. All patients who fulfilled the inclusion criteria gave their informed consent for upper GI tract endoscopy and histologic sampling. The study was approved by the Ethics Committee of both centers. The endoscopic findings were classified as normal, consistent with peptic lesions (in the presence of esophagitis, mucosal reddening with erosions, or ulcers), positive for polyps and/or tumors, suggestive of CD (in the case of a loss or reduction in duodenal folds, a nodular or mosaic mucosal pattern, or duodenal fold scalloping),12,13 or miscellaneous (hiatal hernia, varices, etc). Four duodenal mucosal samples (2 from 2 cm above and 2 from 2 cm below the major duodenal papilla) were obtained from all patients during upper GI tract endoscopy (using GIF-100; Olympus Optical Co, Tokyo, Japan), with further samples being obtained when considered necessary, ie, in the presence of macroscopic appearances consistent with esophagitis, gastritis, and/or duodenitis. The biopsy specimens were oriented, routinely processed, stained with hematoxylin-eosin and periodic acid–Schiff, and blindly examined by two of us (M.T.B. and P.V.) independently. The diagnosis of CD was based on the presence of villous atrophy, crypt hyperplasia, and an increased number of lymphocytes in the epithelium and lamina propria14; the presence of Helicobacter pylori was also always searched for histologically. All patients with a histologic diagnosis of CD also underwent standard nephelometric serological immunoglobulin determinations and IgA antiendomysium antibody measurements obtained by indirect immunofluorescence (Eurospital, Trieste, Italy) and were put on a gluten-free diet and followed up.