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Initial tissue sections from biopsies of endoscopically apparent colonic polyps may not always demonstrate a lesion to account for the clinical findings. Studies have shown that deeper sections and/or reorientation reveal lesions in 10% to 31% of initially nondiagnostic cases. However, many are clinically inconsequential hyperplastic or inflammatory polyps, and, thus, exhaustive efforts to identify them may not be justified. The aim of this study was to identify clinical parameters that predict the detection of adenomas in initially nondiagnostic endoscopic biopsies of colonic “polyps.” We reoriented, reembedded, and obtained deeper tissue levels on 100 initially nondiagnostic biopsy specimens of clinically apparent polyps and found 9% to contain tubular adenomas. Only 3% of polyps smaller than 5 mm proved to be adenomas, compared with 22% of those 5 mm or larger (P < .01). We conclude that nondiagnostic biopsy specimens of polyps measuring 5 mm or more should be further evaluated because they are more likely to represent adenomas, whereas smaller lesions are usually clinically inconsequential.