Although epidermoid cancer of the anus is an uncommon tumor, it has served well as a model for several disciplines within oncology. Advances in understanding the epidemiology and the definitive therapeutic role of combined radiation therapy and chemotherapy for anal tumors have encouraged many investigators to study similar applications in the more common epithelial malignancies. In this monograph, the anatomy of the anal area is reviewed emphasizing the differences in natural history and prognosis between anal margin and anal canal cancers. Treatment does not depend on the specific histologic variant of the epidermoid tumors which arise in this region. The roles of viruses, of immunodeficiency syndromes, and of a history of benign anal disease and trauma in the etiology and epidemiology of this tumor are discussed. Current staging will be critically reviewed stressing that invasive (pathologic) staging by surgery is not indicated, but noninvasive staging has definite limitations. Small superficial tumors may be definitively treated with either limited surgery or radiation. While regional treatments such as surgery and radiation offer cure to between 45% and 60% of nonselected patients, initial treatment with combination radiation and chemotherapy produces cure rates between 65% and 85% for similar groups of patients. The rationale for combined modality therapy is presented and recommendations for therapy by stage of the cancer are made. Finally, we present questions that remain for future research in the clinic and laboratory regarding epidermoid tumors of the anus.