The case of a 63-year-old female patient affected by arterial hypertension under home therapy, with disordered consciousness and confusion, is discussed. At the emergency department of another hospital she underwent cranial CT which showed mild swelling of right cerebral hemisphere. Based on the clinical suspicion of herpes simplex encephalitis compatible with a first MRI examination of the brain, the patient was admitted to the department of infectious disease of the polyclinic to confirm the diagnosis and plan the therapeutic approach. MRI was repeated and completed with EPI-DWI sequences and PRESS spectroscopy. It did not rule out categorically the infectious/inflammatory pattern but, based on a careful evaluation of the anatomic distribution of acute lesions, the most likely diagnostic hypothesis was the presence of multiple watershed cerebral infarcts on the right side.