Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) belongs to a spectrum of EBV-associated lymphoproliferative disease. We present the case of an 89-year-old female with seronegative polyarthritis treated for several years with methotrexate (12.5 mg weekly). She also had asthenia, anorexia and a positive fecal immunohistochemical test. In view of the above, a colonoscopy was performed that revealed a polypoid mass with a malignant appearance in the sigmoid colon, which prevented the passage of the endoscope and was suggestive of colonic adenocarcinoma (CAC).