Diffuse midline glioma (DMG) is one of fatal glioblastoma multiforme (GBM) with no proven medical therapies. Tumor treating fields (TTFields) is a new revolutionary therapy for GBM which prolongs the overall survival time obviously. However, we can observe more tumor growth phenomena (such as distant multiple metastases) than before. This report describes an adult patient who presented headache and dizziness, accompanied by left limb weakness, nausea, and vomiting following car accident trauma, following imaging examinations suggested thalamus GBM. He was treated with subtotal excision. Final pathology was diagnosed as DMG with H3F3A mutation, isocitrate dehydrogenase (IDH) wild type. Following concurrent chemoradiation therapy (CCRT) and adjuvant temozolomide (TMZ) chemotherapy + TTFields therapy were carried out. Supratentorial tumor has been exhibited a partial radiological response for nine months until TTFields was used irregularly or even discontinued in the later stage. Especially, subtentorial and spinal multiple metastasis occurred during this time. Both supratentorial and subtentorial tumors were treated with surgery, radiotherapy, chemotherapy, even targeted drugs, with the only difference being TTFields, but we could see different consequences for tumor growth. One conclusion might be drawn that TTFields can provide a longer survival time (14 8 months reported before) for DMG patients and improve survival benefits. However, we can observe that patients maybe die from subtentorial metastasis because TTFields could not cover the subtentorial tumors, which is the focal challenge at present. So further research on subtentorial tumors with TTFields is urgently needed.