Malignant disease,including mucinous carcinomas of the colorectum,may complicate long-standing Crohn’s disease.An 18-year-old male with extensive small and large bowel involvement with Crohn’s disease developed recurrent peri-rectal fistulous disease that persisted for more than a decade despite pharmacological and surgical therapy as well as later therapy with biological agents. Eventually,an extensive and difficult-to-detect mucinous carcinoma developed in the fistulous tract.Although fistula cancer is rarely described in Crohn’s disease,use of immunosuppressant and biological agents may play an initiating or exacerbating role in its development or progression.As potent biological agents are frequently used, often to avoid surgical treatment,clinicians should have an increasingly high index of suspicion for this potential complication,especially if fistulous drainage persists and remains refractory to medical therapy. Malignant disease, including mucinous carcinomas of the colorectum, may complicate long-standing Crohn’s disease. Ann 18-year-old male with extensive small and large bowel involvement with Crohn’s disease developed recurrent peri-rectal fistulous disease that persisted for more than a decade pharmacological and surgical therapy as well as later therapy with biological agents. Eventually, an extensive and difficult-to-detect mucinous carcinoma developed in the fistulous tract. Although fistula cancer is rarely described in Crohn’s disease, use of immunosuppressant and biological agents may play an initiating or exacerbating role in its development or progression. As potent biological agents are frequently used, often to avoid surgical treatment, clinicians should have an increasingly high index of suspicion for this potential complication, especially if fistulous drainage persists and remains refractory to medical therapy.