Analysis of relative polyp locations in 426 consecutive patients with multiple colonic polyps found on colonoscopy showed novel findings. First, synchronous and metachronous neoplastic polyps showed spatial clustering in individual patients. For example, patients with their largest neoplasm in the cecum or proximal ascending colon, had 34.3 percent +/- 4.6 percent (standard error) of their other colonic neoplasms in the same location. Second, hyperplastic polyps showed spatial clustering in individuals that was statistically significantly greater than expected from the increased hyperplastic polyp concentration in the rectum and sigmoid. Third, hyperplastic polyps showed spatial clustering with neoplastic polyps; this clustering was similar in magnitude to clustering for exclusively hyperplastic or neoplastic polyps. In contrast, lipomas were not spatially clustered with hyperplastic and neoplastic polyps. The magnitude of clustering between hyperplasia and neoplasia showed a closer association between these histologic types than previously appreciated. Because of clustering, regions with prior polyps appear to merit closer surveillance. These findings suggest clinical study, using a randomized controlled clinical trial, of whether a patient who had only rectal and sigmoid adenomas on initial and follow-up colonoscopy should have surveillance with flexible sigmoidoscopy alternating annually with colonoscopy. A patient with a prior cecal adenoma should have surveillance only with a complete colonoscopy or adequate cecal views on barium enema.