Abstract Squamous cell carcinoma of the anal canal is preceded by a spectrum of premalignant lesions known as anal intraepithelial neoplasia (AIN). AIN is caused by infection with the human papilloma virus (HPV), and the pathogenesis mimics that of cervical cancer. It is most commonly associated with HIV infection and high-risk sexual behavior. Symptoms of AIN may mimic benign processes. Multiple screening approaches exist for detecting HPV and dysplasia, but so far there is no standard algorithm. Several treatment options for AIN exist, although recurrence remains high. Regular surveillance by a surgeon is key after successful treatment. Extramammary perianal Paget׳s disease (EMPD) is another premalignant lesion. It is an intraepithelial adenocarcinoma that may or may not be associated with underlying malignancy. There are limited cases reported in the literature, and a staging method has been proposed. Both AIN and EMPD will be discussed in the following chapter.