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In Lynch syndrome, flat and diminutive adenomas are particularly prone to malignant transformation, but they can be missed by standard colonoscopy. It is not known whether chromocolonoscopy is able to detect more adenomas than standard colonoscopy in patients with Lynch syndrome.We conducted a prospective, multicenter, randomized trial to compare standard colonoscopy with standard colonoscopy followed by pancolonic chromoscopy with indigo carmine in patients with a proven germline mutation in a mismatch-repair gene related to Lynch syndrome and who were undergoing screening or surveillance colonoscopy. Standard colonoscopy was used first to detect visible lesions. Colonoscopy with chromoscopy was then performed by a second gastroenterologist (blinded to the findings of the first colonoscopy) to detect additional lesions. The primary end point was the number of patients in whom at least one adenoma was detected.A total of 78 eligible patients (median age, 45 years) were enrolled at 10 centers from July 2008 to August 2009. Significantly more patients with at least one adenoma were identified by chromocolonoscopy (32/78 (41%)) than by standard colonoscopy (18/78 (23%);P<0.001). The percentage of patients in whom at least one additional adenoma was detected during the chromoscopy was 31% (24/78). Overall, chromocolonoscopy plus colonoscopy detected a total of 55 adenomas in 32 patients (mean number of adenomas detected per patient: 0.7 vs. standard colonoscopy alone: 0.3;P<0.001).The results support the proposition that chromocolonoscopy may significantly improve the detection rate of colorectal adenomas in patients undergoing screening or surveillance colonoscopy for Lynch syndrome.