Human papillomavirus (HPV)-associated malignancies other than cervical cancer have increased in recent decades and one of the most challenging is squamous cell carcinoma of the anus (SCCA). This chapter reviews and discusses the recent findings related to anal intraepithelial neoplasia (AIN), the precursor lesion of anal SCC, including grading, terminology, and management of anal dysplastic lesions. A complete discussion of anal carcinoma is beyond the scope of this book, and readers interested in the subject should refer to the specialized literature (Abbasakoor and Boulos, 2005; Shepherd, 2007). Squamous cell carcinoma of the anus (SCCA) and perianal skin is relatively uncommon, accounting for about 4% of all lower gastrointestinal cancers in the United States. However, evidence shows that the incidence of both anal SCC and AIN is increasing in both genders, particularly in high-risk groups such as individuals infected with the human immunodeficiency virus (HIV) and immunosuppressed patients. The prevalence of AIN in surgically removed perianal/anal warts is higher than previously reported. In a recent retrospective analysis, McCloskey et al. (2007) found an overall AIN rate of 33% (with 20% high-grade AIN) in men without HIV infection and 78% (52% high-grade AIN) in HIV-infected men. In HIV-negative female subjects, the overall rate of AIN in perianal/anal warts was 8.3%, with high-grade AIN present in 2.8% of specimens. According to the investigators, the presented data support the judicious pathological analysis of all HPV-related lesions removed from the anogenital region.