The malignant transformation of chronic fistula in ano is rare, accounting for 3% to 11% of all anal canal malignancies. It results from long-standing inflammation and chronic irritation. No guidelines are available for the management of these cases. We herein present a case report of a 55-year-old man who presented with a history of constipation, perianal pain, and discharging fistula in ano of 4-year duration and underwent fistula surgery with recurrence. Biopsy of the fistulous tract revealed adenocarcinoma. He received neoadjuvant chemoradiotherapy, followed by abdominoperineal excision including excision of the fistulous tract. After 18 months of follow-up, he is free of recurrence. We present this case with a review of the literature, highlighting the management strategies.