Headache with neurological deficit and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) syndrome is an important diagnosis to consider in patients presenting with the relevant features to acute medicine. Investigations should aim to exclude more serious differential diagnoses such as infectious, inflammatory and neoplastic causes prior to making a formal diagnosis of HaNDL. Increased awareness and early consideration of HaNDL would help to avoid unnecessary prolonged courses of antimicrobial therapy and invasive investigations such as cerebral angiography.