A 67-year-old female was admitted to our department with difficulty in speech, disorientation, memory loss and seizures. Blood laboratory tests revealed diabetes insipidus. This patient had been treated with steroids for systemic lupus erythematosus (SLE) for 30 years. Due to this treatment neurological symptoms had been understated causing a long delay in performing ulterior researches. A brain MRI revealed a mass lesion in the hypothalamic area. A biopsy was performed and histopathological diagnosis was malignant large B cell lymphoma. Subsequently, she received methotrexate therapy but died of pneumonia during the second cycle. Primary central nervous system lymphoma in association with SLE is a rare occurrence but it should be considered in the diagnostic process when neurological symptoms occur. A brain MRI must be performed and corticosteroids should be interrupted. A biopsy of the cerebral mass lesion permits diagnosis and appropriate therapy may be administered.