Anal squamous cell carcinoma (SCC) is a rare malignancy of the digestive tract involving the anorectum and anus accounting for <3% of all digestive system cancers. Most anal SCC is associated with infection by a high-risk HPV serotype and disease can be prevented through vaccination. These cancers are best managed by a multidisciplinary team including oncologists, radiation oncologists, and surgeons. Most anal SCC responds to radiation and chemotherapy; however, in select patients, surgical resection may be offered or necessary depending on the initial staging or failure to respond to chemotherapy and radiation. Following treatment of the primary lesion, patients should continue surveillance for disease recurrence for 5 years; in high-risk populations, some guidelines advocate for life-long surveillance every 3–6 months for evidence of disease recurrence.