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Background & Aims: There are limited data describing the performance of Fuji Intelligent Color Enhancement (FICE, EC 590 ZW; Fujinon Inc, Saitama, Japan) for differentiating polyp histologies during screening colonoscopy. We evaluated the ability of an endoscopist to diagnose small polyp histology during a screening colonoscopy using FICE., Methods: A prospective study was performed on 763 consecutive, asymptomatic subjects who were undergoing screening colonoscopy. Pit patterns and vascular patterns were used to predict the histology of 525 polyps (mean size, 4.5 ± 2.2 mm, 315 adenomas) of less than 10 mm using FICE with high magnification and without. The performances of the FICE analyses were calculated and compared with the results from the histopathology., Results: The overall accuracy achieved by FICE with high magnification in the diagnosis of adenomas of less than 10 mm (87.0%) was significantly greater than that achieved without high magnification (80.4%; P < .05). Moreover, the improvement of accuracy attained when using high-magnification FICE was most pronounced and significant compared without using high-magnification FICE in the diagnosis for diminutive polyps (≤5 mm; 85.4% vs 79.1%; P < .05). Among all types of adenomas, the sensitivity of FICE was lowest for sessile serrated adenomas (38.5% vs 89.4%; P < .01), even when FICE was used with high magnification., Conclusions: FICE with high magnification is better for differentiating the histology of small polyps during screening colonoscopy than FICE without high magnification, especially for diminutive polyps. Large-scale studies are needed to improve the identification of serrated adenomas and small diminutive polyps using FICE., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)