To delineate the causes of death (COD) in adults with supratentorial glioblastoma multiforme (GM) we reviewed 117 consecutive cases examined at autopsy over a nineteen year period at the University of Washington. Twenty cases (17%) had expired unexpectedly without ante mortem diagnosis, 5 patients (4%) had been diagnosed as having lower grade astrocytomas prior to death. Other than the 20 patients without ante mortem diagnosis, all patients had a surgical procedure for treatment and/or diagnosis (biopsy 10%, craniotomy 90%). Postsurgical therapy varied, but there was no significant difference in median length of survival among the different treatment groups. Factors considered as potential COD were: herniation (axial, transtentorial, subfalcine, tonsillar), surgical complications (death within thirty days of surgery secondary to cerebral hemorrhage and/or edema), severe systemic illness, brainstem invasion by tumor, and neutron-induced cerebral injury (cerebral and brainstem gliosis were evident in these cases). A potential COD could be identified in 93% of patients. Patients with no ante mortem diagnosis were likely to have herniated (p = 0.01), whereas patients who underwent neutron irradiation were unlikely to have herniated (p = 0.001). No other variables were statistically significant predictors of herniation, including multifocal tumors (20 patients), and brainstem invasion by tumor (18 patients). No patients died as a result of treatment except those who underwent neutron radiotherapy and those who died postoperatively. Although significant mass effect, as evidenced by herniation, was apparent in 61% of patients, most of these patients had an additional identifiable COD. We conclude that the COD in patients with GM varies and is multifactorial.