Background: Orthostatic hypotension (OH) is the key manifestation of autonomic dysfunction with many causes. Systemic neurological causes such as paraneoplastic syndrome are usually ignored. Methods: We retrospectively analyzed clinical and examination data of 2 patients who were hospitalized, with onset symptom of OH and who were diagnosed as paraneoplastic syndrome. Results: The patients were characteristic of an initial symptom of OH, positive anti-Hu antibody and albuminocytologic dissociation in the cerebrospinal fluid. Patient 2 died and Patient 1 worsened during follow-up. Conclusions: The diagnosis of paraneoplastic syndrome is usually neglected when the onset symptoms are autonomic dysfunctions such as OH. Neurologists should improve their knowledge to diagnose accurately.