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Adult-onset dermatomyositis (DM) is a rare disease, characterized by muscle weakness, increased serum enzymes, evocative electromyogram and typical histological pattern. We present the case of a 63-year old female patient who was recently diagnosed with DM. The administration of a single low-dose methotrexate (15 mg subcutaneous) induced pancytopenia and nephrotic syndrome. Drug toxicity was reversible with adjunctive therapies and supportive measures. Further immunosuppression was switched to mycophenolate mofetil with good response. Despite worldwide frequent use, physicians should be aware of MTX remaining toxicity and prevent side effects occurrence.