Glatiramer acetate (GA), a well tolerated immunomodulatory treatment for relapsing-remitting multiple sclerosis (RR-MS), consists of a 4-amino acid polymer that mimics the myelin basic protein (MBP). We report the first case of biopsy-proven erythema nodosum (EN) in a patient presenting RR-MS under GA treatment. Comprehensive exams were negative in the search of the etiology of EN, which spontaneously resolved despite treatment continuation. GA treatment is known to generate reactive polyclonal antibodies that can cross-react with myelin epitopes, like MBP. These antibodies may also be implicated in allergenic reactions and auto-immune adverse events, such as anaphylactic shock, lymphadenopathy, livedo-like dermatitis, or lymphocytic infiltration. EN is an unspecific skin reaction occurring in several disorders and induced by many treatments. As EN can result from a polyclonal antibody response or type I hypersensitivity mechanisms, we hypothesize that GA treatment could be responsible for the occurrence of EN.