Context. - Glioblastoma (GBM), the most common primary intracranial malignancy, is a morphologically diverse neoplasm with dismal prognosis despite multimodality therapy. Only 3 distinct morphologic variants of GBM are currently recognized by the current World Health Organization classification scheme, including GBM, giant cell GBM, and gliosarcoma. Additional variants, some of which have significant morphologic overlap with tumors that have more favorable prognosis and treatment response rates, particularly anaplastic oligodendroglioma, have been described since its publication in 2000 and may be included in the next classification. Objective. -To summarize the morphologic and molecular genetic diversity of both well-established and novel GBM variants and outline our approach to these heterogeneous neoplasms and their distinction from other diffuse, high-grade gliomas. Data Sources. - Published literature and our own experience in an active academic diagnostic surgical neuropathology practice were reviewed. Conclusions. - Precise subclassification of GBM is required for accurate prognostication and appropriate treatment planning.