Long term survival is rare in patients with glioblastoma multiforme (GBM). To determine if the tumors of patients with long survivals constitute a subgroup of patients with identifiable molecular genetic characteristics, we studied the p53 gene and Epidermal Growth Factor Receptor (EGF-R) expression in long-term survivors of GBM. A review of the Tumor Registry of Memorial Hospital for Cancer and Allied Diseases documented that 521 patients were treated for GBM between 1954 and 1987 and that 12 patients had seven-year or longer survivals. Six additional long-term survivors were identified from other institutions. After pathological re-examination, the diagnosis of 8 of these 18 (44%) tumors was changed to other histologic tumor types. Using immunohistochemical analysis, 4 of 10 confirmed malignant gliomas had over-expression of p53. Polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis and sequence analysis of these 4 tumors showed no p53 mutations in exons 5-8, the region where most mutations have been reported in human malignancies. Immunohistochemical analysis for EGF-R was performed on the tumors of the 10 long-term survivors. EGF-R over-expression was identified in 4 (40%), which is consistent with previous reported studies for GBM in general. These findings suggest that there is a subset of GBM defined by the accumulation of wild-type p53 and that the over-expression of EGF-R does not preclude long-term survival. The seven-year survival rate for confirmed GBM in patients from the Memorial Hospital Tumor Registry was at least 1%.