A 47-year-old woman with a 2-year history of rheumatoid arthritis (RA) undergoing methotrexate treatment developed a perforated ulcer in the ileum for which she underwent emergency surgery. A histological analysis of the extirpated specimen presented a possible Epstein-Barr virus (EBV) infection in the ulcerative lesion without a feature of lymphoproliferative disorder. Interestingly, the patient's serological tests with a paired serum diagnosed a primary EBV infection. The present case emphasizes the importance of being aware of severe enteritis as a possibility for patients with RA, for an accurate diagnosis.