Despite an improved understanding of the molecular aberrations that occur in glioblastoma, the use of molecularly targeted therapies have so far been disappointing. We present a patient with three different brain tumours: astrocytoma, glioblastoma and gliosarcoma. Genetic analysis showed that the three different brain tumours were derived from a common origin but had each developed unique genetic aberrations. Included in these, the glioblastoma had PDGFRA amplification, whereas the gliosarcoma had MYC amplification. We propose that genetic heterogeneity contributes to treatment failure and requires comprehensive assessment in the era of personalised medicine.