OBJECTIVE To investigate the natural history of fast developing esophageal and cardia precursors.METHODS Repetitive endoscopic screenings were performed among 40-69-year-olds in the high-incidence areas for esophageal cancer in Shexian.RESULTS The initial diagnosis and the lag-time for 7 subsequently identified severe dysplasia (SD) subjects were as follows: in one subject 13 months after a baseline diagnosis of normal epithelium, in another subject 7 months after a baseline diagnosis of base cell hyperplasia (BCH), in four subjects 3,4,4, and 10.5 months after baseline diagnosis of mild dysplasia (mD), and in one subject 12.5 months after a baseline diagnosis of moderate dysplasia (MD). The initial diagnosis and the lag-time for 6 subsequently identified carcinomas in situ or intramucosal carcinoma cases were: in one case 48 months after a baseline diagnosis of mD, in 2 cases 4 and 13 months after baseline diagnoses of MD, and in the other 3 cases 3.5, 9, and 17.5 months after baseline diagnoses of SD. The initial diagnosis and lagtime for 3 subsequently identified invasive cancer cases were: in one case 50 months after a baseline diagnosis of MD, in 2 cases 14 and 19 months after baseline diagnoses of SD. In addition, during a 4-year-follow-up of 18 subjects after endoscopic mucosa resection, 9 of them were found to have developed precursors again at other sites, and also additional findings were obtained for 11 of the 16 dysplasia cases by repetitive biopsy in less than 2 months after the initial endoscopy.CONCLUSION A 5-year screening interval for BCH and mD, and a 3-year interval for MD may be too long for the fast developing precursors. Periodic screenings with shorter intervals should be considered to control the number of interval cases due to fast development, multifocal carcinogenesis, and false negative results inherent in one-time endoscopic biopsy sampling.