Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing to the development of various tumors (central nervous system and retinal hemangioblastomas, endolymphatic sac tumors, renal cell carcinoma and/or renal cysts, pheochromocytomas, pancreatic cysts and/or tumors). Incidence of the disease is 1/36,000. Central nervous system hemangioblastomas and renal cell carcinoma are the main causes of death. The VHL gene, located on chromosome 3p25-26, is a tumor-suppressor gene encoding for a 213 amino acid protein which plays a major role in regulation of VEGF expression. Germline mutations of the VHL gene are identified in about 75-80% of the patients. Somatic mutations of the VHL gene are found in both sporadic central nervous system hemangioblastomas and sporadic "clear" renal cell carcinomas. For neurosurgeons search for VHL disease should be imperative in presence of a patient with apparently "sporadic" central nervous system or endolymphatic sac tumor.