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The incidence of anal cancer is increased in men with a history of anal receptive intercourse. Analogous to cervical cancer, whose precursor is cervical high-grade squamous intraepithelial lesion (HSIL), anal cancer may be preceded by anal HSIL. Although not yet proven, detection, follow-up, and treatment of HSIL may prevent development of anal cancer. Cervical colposcopic methodology was used to describe anal lesions and to determine if HSIL could be distinguished from low-grade squamous intraepithelial lesion (LSIL).The colposcopic characteristics of 385 biopsied anal lesions were described and correlated with results of histopathology in a cohort of 121 human immunodeficiency virus-positive and 31 human immunodeficiency-negative homosexual/bisexual men with anal lesions followed as part of a longitudinal study of anal squamous intraepithelial lesions. Color, contour, surface, and vascular patterns of anal lesions were analyzed and correlated with histologic diagnosis.Sixty-seven percent of biopsies showed LSIL and 26 percent showed HSIL. The positive predictive value for anal HSIL in lesions with characteristics typical of cervical LSIL was 7.7 percent (95 percent confidence interval, 1.8-14), whereas the positive predictive value for anal HSIL in lesions with characteristics typical of cervical HSIL was 49 percent (95 percent confidence interval, 40-58).The colposcopic appearance of different grades of anal squamous intraepithelial lesions was similar to those described for the cervix. Incorporation of colposcopy into assessment of anal disease could aid in distinguishing anal LSIL from HSIL.