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Most adult glioblastoma multiformes (GBMs) present in patients 45–70 years old; tumors occurring at the extremes of the adult age spectrum are uncommon, and seldom studied. We hypothesized that young-adult GBMs would differ from elderly-adult and from pediatric GBMs. Cases were identified from years 1997 to 2005. Demographic and histological features, MIB-1 and TP53 immunohistochemical findings and epidermal growth factor receptor (EGFR) amplification status by fluorescence in situ hybridization were compiled and correlated with survival. Twenty-eight (74%) of our 38 young-adult GBM patients had primary de novo tumors, two of which occurred in patients with cancer syndromes. Two additional GBMs were radiation-induced and eight (21%) were secondary GBMs. Seven patients were identified as long-term (>3 years) survivors. Six of 38 cases manifested unusual morphological features, including three epithelioid GBMs, one rhabdoid GBM, one gliosarcoma and one small cell GBM containing abundant, refractile, eosinophilic inclusions. MIB-1 index emerged as the most important prognosticator of survival (P < 0.005). Although there was a trend between extent of necrosis, TP53 immunohistochemical expression, and EGFR amplification status and survival, none reached statistical significance. GBMs in young adults are a more inhomogeneous tumor group than GBMs occurring in older adult patients and show features that overlap with both pediatric and adult GBMs.