Although the c-Myc oncogene is frequently deregulated in human cancer, its involvement in the pathogenesis of glioblastoma is not clear. We conducted immunohistochemical analysis of the expression of c-Myc, polycomb ring finger oncogene (BMI1), and acetylation of the lysine 9 (H3K9Ac) of histone 3 in 48 patients with glioblastoma who underwent surgery followed by radiotherapy and temozolomide treatment. The expression of c-Myc, BMI1, and H3K9ac was correlated with clinical characteristics and outcome. We found that overexpression of c-Myc was significantly associated with that of BMI1 (P = .009), and that patients who harbored glioblastomas overexpressing c-Myc and BMI1 showed significantly longer overall survival (P < .0001 and P = .0009, respectively). Our results provide the first evidence of the prognostic value of c-Myc and associated genes in patients with glioblastoma. The favorable effect of c-Myc and BMI1 expression on survival is likely mediated by the sensitization of cancer cells to radiotherapy and temozolomide through the activation of apoptotic pathways.