Anal fistulas are frequent events which often recur after an inadequate surgical treatment. Nevertheless their evolution into malignant diseases is infrequently observed. The authors report one case of mucinous adenocarcinoma arising out of a recurrent, long-lasting fistula-in-ano. As reported, abdomino-perineal resection combined with radiotherapy can be the choice treatment. The difficulty is to obtain a reliable differential diagnosis. No imaging technique nor histologic examination can establish a definitive reliable diagnosis; nevertheless, as the risk of adenocarcinoma developing from a long-lasting recurrent fistula-in-ano, although small, is real, authors believe that operative exploration and biopsy of recurrent abscesses and fistulas should be recommended.