A 44-year-old right-handed Caucasian male was initialy diagnosed in 2007 with dermatomyositis (DM) and in 2009 with systemic lupus erythematosus (SLE) (overlap syndrome). He was treated with Methylprednisolone and Hydroxychloroquine. He interrupted the treatment in the last three years. The patient presented with fever (39.8 degrees C), left zoster ophthalmicus, headache and psychomotor agitation. The cerebral CT scan showed left hemispheric hypodense lesions. Herpetic encephalitis was suspected. The patient was referred to the Institute of Infectious Diseases. The patient's neurological status worsened, he presented spastic tetraparesis and aphasia. DW-MRI, ADC, DS and AngioMRI were done, the patient proved to have an ischemic stroke due to acute thrombosis of the left internal carotid artery and multiple watershed infarctions. An infectious pathology, including HSV-1, was excluded by PLEX ID performed from CSF. Acyclovir, anti vitamin K, steroidal intravenous pulse therapy was started. The patient was referred after two weeks to the Department of Neurology. Mild inflammatory syndrome, tests for anti-double stain DNA (dsDNA), anti-Sm, anti-SSA, IgM and IgG anti-cardiolipin antibodies and lupus anticoagulant were positive. He was currently treated with Methylprednisolone (48 mg/d), anti vitamin K, statin, symptomatics. The outcome was favorable, with good laboratory response. Overlap syndrome may be associated with a significant increase in the risk of stroke. Our case presented without clinically susceptible symptoms of stroke but found to have stroke after neurological assessment associated with overlap syndrome (DM and SLE).