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Patients with systemic lupus erythematous (SLE) are at higher risk of malignant lymphomas, particularly non-Hodgkin lymphoma. Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma. In adults, about twenty cases have been reported. Malignancy in pediatric-onset patients with SLE has been less extensively studied. Herein, we report the first case of PCNS lymphoma in an adolescent diagnosed with lupus nephritis treated with Mycophenolate Mofetil.