The finding of prolonged survival with HER2 inhibition in women with HER2-positive metastatic breast cancer21–25 and the increased permeability of novel HER2 inhibitors into the brain26 have led to an interest in HER2-targeted therapy as a treatment of IMD from HER2-positive metastatic disease.16,27 Guidelines from the National Comprehensive Cancer Network,18 Congress of Neurological Surgeons,17 and European Association of Neuro-Oncology19 reflect the paucity of evidence to support or condemn the use of HER2-targeted therapy for IMD. This evidence concerns the gene ERBB2 and metastatic neoplasm.