Anal margin cancers arise from skin lateral to the intersphincteric groove and are usually well-differentiated, keratinized variants of squamous cell carcinoma, which rarely metastasize, compared to anal canal cancers. Other lesions in this area are Bowen disease, basal cell carcinoma, melanoma, verrucous carcinoma, and Paget disease. Bowen disease and Paget disease can present as a persistent pruritic rash. Basal cell carcinoma has raised edges with central ulceration and is often mistaken for a fissure or chancre. Verrucous carcinoma may present as a slowly growing invasive cancer in long-standing large condyloma acuminata. Melanomas in the perianal area are frequently amelanotic and carry a very poor prognosis, with most patients succumbing to distant disease. The differential diagnosis includes numerous benign diseases and dermatoses like fungal infection and psoriasis. The importance of a high index of suspicion is critical to prevent the frequent delay in diagnosis. A biopsy is diagnostic.