In summary, our study shows that (i) HOTAIR is highly expressed in a subset of malignant gliomas, independently of gene copy number alterations; (ii) epigenetic marks at the level of DNA methylation in particular CpG sites associate with HOTAIR levels in GBM; (iii) co-expression of HOTAIR and HOXA9 occurs frequently in high-grade glioma, but not in other cancer types; (iv) HOTAIR is prognostically valuable in malignant glioma patients; and (v) HOTAIR and HOXA9 may be useful biomarkers to integrate a molecularly-based stratification of GBM patients. Here, HOTAIR is linked to glioblastoma.