Methotrexate is a folic acid antimetabolite and an immunosuppressive agent. The folic acid synthesis inhibition reduces cell proliferation. It has been used to treat autoimmune diseases such as rheumatoid arthritis, or as part of chemotherapy against several types of cancer. Its use can produce a wide variety of adverse effects, among which we find Oral Mucositis. This constitutes a loss of the integrity of the mucosa, thus representing a gateway for microorganisms of the oral microflora, predisposing patients to infection, especially during periods of neutropenia.We describe two clinical cases: The first, is a female patient with a diagnosis of rheumatoid arthritis of 40 years of evolution. She was medicated with Methotrexate, showing several oral lesions and was referred to the family doctor with a presumptive diagnosis of Methotrexate mucositis. Twenty days after the drug was suspended, the evolution was favorable.