The past few years have seen remarkable progress in understanding the molecular genetic basis of glioma formation. Affected oncogenes and tumor suppressor genes have been identified and putative tumor suppressor loci have been mapped. These studies have illustrated distinct molecular pathways for different glial neoplasms. We summarize the findings of an ongoing study initiated to characterize human gliomas on a molecular basis. The data are compiled from 150 astrocytic, oligodendroglial, and mixed gliomas that were assessed for genomic alterations characteristic of these neoplasms, i.e., loss of portions of chromosomes 1p, 9p, 10, 17p, 17q, and 19q, mutations of the p53 tumor suppressor gene, and amplification of the EGF receptor (EGFR) gene. Our findings support the hypothesis that distinct genetic pathways result in the formation of astrocytic and oligodendroglial neoplasms of different malignancy grades, and that glioblastoma multiforme may be subdivided into genetically distinct subsets. Such findings may not only lead to a better understanding of neoplastic transformation in glial cells, but may also have a major impact on clinical neuro-oncology.