Anal carcinomas account for 1-2% of all digestive tract cancers. They may occur in the anal canal, perianal region (up to 5cm) and surrounding skin. Squamous cell carcinoma (SCC) is the most frequent type (80%). In the last decades, the incidence of anal SCC has increased in relation with the human immunodeficiency virus (HIV) infection, especially in men who have sex with men (MSM). Individuals with impaired immunity, such HIV positive, are at higher risk of perianal diseases, which has not been altered by the introduction of highly active antiretroviral therapy. SCC arising from a perianal fistula is rare. We report a rare case of a large squamous cell carcinoma arising from a perianal fistula, in a HIV positive patient, successfully treated with chemo-radiotherapy alone with no late toxicity. Long standing perianal fistula often causes late diagnosis of perianal carcinoma. A previous history of HIV positive may increase the index of suspicion for malignancy.