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Glioblastoma (GB) is the most common type of malignant tumor of the central nervous system and, despite extensive research, its prognosis is poor. Although recent advances have been made in the treatment of GB with aggressive resection combined with radiochemotherapy, more than three-quarters of GB patients succumb to the disease within two years. The current study presents a highly aggressive case of small cell GB as diagnosed by histological features and immunohistochemistry for vimentin, glial fibrillary acidic protein, oligodendrocyte lineage transcription factor 2, isocitrate dehydrogenase 1-R132H and p53. The patient was treated using a multidisciplinary treatment strategy, which included temozolomide, CyberKnife radiotherapy and autologous formalin-fixed tumor vaccination. In addition, the patient developed radiation necrosis, which was treated with bevacizumab. In conclusion, three years following the initial diagnosis, the patient continues to experience a successful clinical course, and the observations of the current study demonstrate that a multidisciplinary treatment strategy may be effective for the treatment of aggressive GB. [ABSTRACT FROM AUTHOR]