Hemangioblastoma may arise in isolation ("sporadic" cases) or as a major manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder with a prevalence of at least 1/36,000. In addition of central nervous system hemangioblastomas (cerebellum, spinal cord and retina), affected patients may develop renal cysts or carcinomas, pheochromocytomas and pancreatic cysts. A multidisciplinary group including neurosurgeons, geneticists, pathologists and clinicians from all involved specialities has been organized to develop a national registration of all hemangioblastoma and VHL patients. The findings of a preliminary 10-year study (1983-1993) conducted in France are presented. Two hundred thirteen cases of hemangioblastoma were reviewed for their location and genetic features. The majority (77%) of the tumors were located in the cerebellum whereas 23% were located inside the spinal canal. By thorough clinical examination of the patients and systematic genetic inquiry of their family background, it was found that 34.3% of the total (58.7% before age 30) were afflicted with VHL disease. Spinal hemangioblastomas were more often related to VHL disease than infra-tentorial locations (50% versus 36.6%). In addition, mean age at diagnosis in VHL disease was significantly younger than in sporadic cases (33.5 +/- 10 versus 43.6 +/- 15 years). Recent progress in VHL molecular genetics led to the identification of the mutated gene to the distal part of the short arm of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and, hopefully, to elucidation of pathogenesis, which may offer a further glimpse into tumorigenesis in general. Because of the usually early adulthood onset, accurate presymptomatic diagnosis of affected members would be of great benefit to VHL families. However, the fact that very few mutations in the VHL gene are identified precludes molecular diagnosis of "sporadic" hemangioblastomas. In summary, this study reveals that VHL-related hemangioblastoma is a more common clinical problem that it was previously reported. Thus, all patients with an apparently isolated central nervous system hemangioblastoma should be investigated for evidence of VHL disease.