In recent years, results from molecular-based investigations of central nervous system neoplasms have indicated that the occurrence of specific genetic alterations correlates with tumor malignancy and clinical behavior. One such example is epidermal growth factor receptor gene amplification and alteration in association with tumors histologically classified as glioblastoma multiforme. As our understanding of the implications of these changes develops, detection of epidermal growth factor receptor alteration and amplification may have diagnostic, prognostic, and ultimately, therapeutic value. The goal of this communication is to demonstrate the usefulness of stereotactic specimens for molecular genetic analysis, in this case, the analysis of the epidermal growth factor receptor gene for amplification and alterations. The techniques used here will maximize the number of cases from which useful information can be obtained. Properly adapted, the value of these techniques for expanding our understanding of these lesions is enormous.