Anal cancer screening programs are gaining momentum within the United States and Europe. The goal of such programs is to detect and eradicate human papillomavirus (HPV) related intraepithelial lesions of the anal canal before progression to invasive squamous cell carcinoma occurs. Programs are designed to screen the anal-rectal transformation zone of a highly selected group of at-risk patients using exfoliative cytology techniques, comparable to the cervical Pap test. Patients with abnormal cytology results should be referred for anoscopy, during which the anal-rectal mucosa will be carefully visually inspected by a qualified physician. Abnormal areas are biopsied for definitive histological diagnosis, and treatment should be offered as appropriate. A comprehensive anal cancer screening program should offer screening, anoscopy when indicated, and treatment for affected patients as clinically appropriate.