Although primary intracranial neoplasms are the most common type of solid cancer in children, little is known about their etiology at the molecular genetic level. Recently, studies have shown that a class of genes known as tumor suppressors play an important role in the origin of several different types of human tumors, including those located in the central nervous system (CNS). Using a variety of techniques, selective loss of DNA sequences has been identified in tissue specimens from children with medulloblastoma, one of the most common pediatric brain tumors. The most consistent losses to date have been shown for probes located on distal chromosome arm 17p. Although the known tumor suppressor p53 is located on this chromosome, and deletion and mutation of the p53 gene are the most common genetic events in human cancers of many types, such alterations have been infrequently detected in medulloblastoma specimens. These results suggest that inactivation of another tumor suppressor gene or genes located on 17p is important in medulloblastoma tumorigenesis. Deletion of 17p has also been shown to have implications for clinical management, as the loss of DNA sequences located on this chromosome arm is strongly associated with a negative prognosis for these patients. The identification and cloning of this tumor suppressor gene or genes will aid in understanding of the pathogenesis of medulloblastoma, as well as guiding the development of novel and more effective strategies for a cure.