EGFR mutations have been reported in up to 21% of glioblastoma tumors (GBM). In GBM, EGFR mutations typically cluster in the extracellular domain and include in-frame deletions and missense mutations. However, mutations (such as V774M) in the tyrosine kinase domain of EGFR have been previously reported in GBM. The clinical significance of this mutation with regards to response to TKI therapy in GBM needs further elucidation. Results should be interpreted in conjunction with other laboratory and clinical findings.