Stereotactic biopsy of CNS tumors provides a small amount of tissue for pathologic diagnosis. This potentially leads to inaccurate grading of gliomas because of their histologic heterogeneity. We compared histologic diagnoses in a consecutive series of 329 patients with newly diagnosed anaplastic gliomas whose diagnoses were established by either stereotactic biopsy or open resection. Of 262 patients undergoing resection, 214 (82%) had glioblastomas and 48 (18%) had anaplastic astrocytomas (AAs). Of 67 patients undergoing stereotactic biopsy, 33 (49%) had glioblastomas and 34 (51%) had AAs. This difference suggests that some AAs diagnosed by stereotactic biopsy are actually glioblastomas and has important implications for the design and interpretation of clinical trials.