To assess the evolution of gastric epithelial dysplasia (GED), a prospective multicenter study was based on a protocol of repeated endoscopies and biopsies. To date, 134 cases (0.4% of all patients endoscopically examined in the same period) have been diagnosed as having GED and 80 of those have had an "adequate" follow-up (at least three endoscopies). Mean follow-up time was 18 months. Gastric epithelial dysplasia was mild in 59% of cases, moderate in 25%, and severe in 10%. Six percent of the patients had lesions that were "indefinite for dysplasia." Chronic atrophic gastritis (40%), gastric ulcer (32%), gastrectomy (10%), and polyps (9%) were the most frequently associated lesions. The term "regression" was adopted for GED no longer detectable during follow-up and the term "progression" was used when more severe changes or cancer was detected. Mild GED regressed in 66% of cases, persisted in 15%, and progressed in 19% (three cases to moderate, one to severe, and five to cancer). Moderate GED regressed in 30% of patients, persisted in 30%, and progressed in 40% (one to severe GED and seven to cancer). Severe GED regressed in 12.5% of patients, persisted in 12.5%, and progressed to cancer in 75%. Of the five patients with lesions indefinite for dysplasia, two had no dysplastic changes at follow-up and three had cancer diagnosed. Ten of 21 cases of cancer (48%) were at the early stage. The diagnosis was reached within the first year of follow-up in 14 cases and after 1 year in seven (13 to 39 months). Fifteen of 21 cases of cancer were diagnosed in gastric ulcer patients. In conclusion, GED is an infrequent finding and its biologically neoplastic significance is confirmed by the results of the follow-up study: (1) in its mild form, it tends to regress but adequate subsequent check-ups are mandatory as it may associate with or evolve as cancer; (2) patients with moderate GED require strict follow-up since the lesion shows a higher cancer risk; (3) surgery is indicated for severe GED because gastric cancer develops in 75% of cases; and (4) patients with lesions indefinite for dysplasia should immediately undergo repeat endoscopy and biopsy. Such an approach allows gastric cancer to be detected at an early stage in a much higher percentage of cases than may be expected.