The aim of this study was to assess survival and prognostic factors of 98 consecutive patients with unresectable glioblastoma multiforme (GBM) after stereotactic biopsy. Patients were diagnosed between 1993 and 1998, and the treatment modality subsequent to stereotactic biopsy was determined by the year of diagnosis. Before 1995, patients did not receive further specific therapy after stereotactic biopsy (n=36). In 1996, patients were administered radiotherapy starting within 6 weeks after stereotactic biopsy (n=24). From 1997 to 1998, patients received combined radio-/chemotherapy (RCT; CCNU orally) starting within 2 weeks after stereotactic biopsy (n=38). Patients' age ranged from 21 to 84 (median 64) years and their median Karnofsky performance score 2 weeks after stereotactic biopsy was 80 (range 60–100). Survival and prognostic factors were analyzed with respect to administered treatment modalities (without specific therapy versus radiotherapy versus combined RCT), with respect to age (>/≤50 years), gender, Karnofsky performance score (≥/<80), tumor location (frontal, parieto-temporal, central, occipital) and tumor size (>/≤5 cm; tumor multiplicity was considered as diameter >5 cm) by the Kaplan–Meier method, by log-rank test and multivariate Cox regression analysis. Post-biopsy treatment modality was the strongest predictor for survival. Median (range) survival was 9 (3–47) weeks in those without specific therapy, 13 (5–54) weeks in patients receiving radiotherapy and 31 (11–101) weeks in patients receiving combined RCT (p≤0.001). Age≤50 years (p≤0.05) in addition to tumor size in multivariate Cox analysis were found to be of significant influence onto survival, too. Combined RCT could be performed on a complete outpatient basis. Toxicity consisted of mild asymptomatic thrombocytopenia. We conclude that the administration of combined RCT within a minimum interval after stereotactic biopsy yielded a significant increase in survival. Patients' acceptance was excellent. These results encourage us to treat even patients with unresectable GBM with combined RCT.