In an attempt to characterize the natural history of the gastric precancerous process, 1422 residents of a high risk area of Nariño, Colombia, have been followed from 3–16 years (average 5.1) with repeated gastric biopsies, for a total of 7290 person-years. The original cohort consisted of 1788 individuals yielding a successful completion rate of 79.5%. Comparison of initial and subsequent biopsies revealed a very complex dynamic flow of both progressive and regressive events, suggesting sporadic environmental forces of modulation. One-time measurement of gastric juice, pH, and nitrite failed to predict future events in the gastric mucosa. The net loss of individuals whose gastric mucosa initially showed normal histology or superficial gastritis was 3.3%/year, representing a net gain of 1.7% for chronic atrophic gastritis, 0.9% for intestinal metaplasia, and 0.7% for dysplasia. The incidence rate of gastric cancer in this population was 0.16/100 person-years. The net rates of progression were higher and those of regression lower in older compared to younger individuals. The general pattern detected is that of a slow forward movement in the previously described hierarchical organization of precursor lesions. The presence of progressive as well as regressive changes and the slow pace of change offer special opportunities to inhibit progression through intervention strategies targeting previously identified etiological factors. The difficulties and opportunities offered by the long term follow-up studies as well as the congruency of the findings with current etiological hypotheses are discussed.