Adenomatous polyps are common neoplastic lesions of the large intestine. The risk of carcinoma increases with polyp size. Small polyps are typically totally embedded for histologic examination, but no standard method for sampling large, grossly benign polyps has been established. We reviewed grossly noninvasive adenomas 2.5 cm or larger to determine the percentage that contained high-grade dysplasia (HGD) and invasive cancer (IC). Based on these findings, we suggest an approach to evaluating large adenomas. Forty-three colon resections met the inclusion criteria (no previous diagnosis of cancer, no gross evidence of invasion, and totally embedded polyp). Twelve (28%) had HGD with 3% (1 of 33 slides) to 100% (4 of 4 slides) containing HGD. Five (12%) had IC with 4% (3 of 72 slides) to 42% (5 of 12 slides) containing IC. All cases with IC had HGD in other slides. Probability studies showed that in the majority of cases, polyps would need to be entirely embedded to have an estimated probability of 95% or more of detecting either HGD or IC. Therefore, grossly noninvasive adenomas should be routinely entirely embedded.