The Epstein-Barr virus (EBV)-positive mucocutaneous ulcer is a benign lymphoproliferative disorder first reported by Dojcinov et al. in 2010, defined as a mucosal or cutaneous ulcer that is histologically characterized by a polymorphous lymphoid infiltrate containing proliferating EBV-positive atypical large B cells and/or Hodgkin/Reed-Sternberg-like cells. Although it may histologically resemble diffuse large B-cell lymphoma, this entity presents an indolent clinical course. Patients are usually immunosuppressed due to different causes, including organ transplantation, age-related immunosenescence, human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), among other iatrogenic immunosuppressions. Many cases have been reported associated with the use of methotrexate (MTX) therapy for different rheumatological conditions. Females are usually more affected, and most of the individuals are elderly patients. The lesion usually manifests as a well-circumscribed, shallow, isolated ulcer in the oral and oropharyngeal mucosa, skin, and gastrointestinal tract, and clinical follow-up is very important and necessary for diagnostic confirmation of EBV-positive mucocutaneous ulcers, since the lesion may spontaneously regress and heal after some weeks upon reduction of immunosuppression.