Over the past few years, although much has been learned about the molecular genetics of central nervous system (CNS) tumors, researchers and pathologists are only beginning to understand the scientific basis of the development of these tumors. Data accumulated so far support the division of glioblastoma into two clinical and molecular subsets. Primary or de novo glioblastomas occur in older patients, are clinically aggressive and exhibit epidermal growth factor receptor amplification or overexpression. Secondary glioblastomas develop from pre-existing low-grade astrocytomas, have a more protracted clinical course, and frequently contain p53 mutations. Both types of tumors show deletions of chromosome 10 and possibly mutations of the PTEN/MMAC1 gene as an endstage event. Oligodendrogliomas have been shown to have genetic abnormalities distinct from those of the astrocytic tumors, commonly involving chromosomes 1p and 19q. As regards meningiomas, loss of chromosome 22q and mutations of the neurofibromatosis type 2 gene are frequent events and loss of chromosome 14q and 10q may be seen in atypical or malignant transformation. Such genetic findings, apart from providing a better understanding of neoplastic transformation in brain tumors, are beginning to form the basis of a new approach to neuro-oncology.