AbstractBackgroundEmbryonal tumor with multilayered rosettes (ETMR) is a deadly grade IV pediatric brain tumor. Despite an intensive multimodal treatment approach that includes surgical resection, high‐dose chemotherapy, and radiotherapy, the progression‐free survival at 5 years is less than 30%.CaseWe report a case of long‐term survival in a 5‐month old female with a large mass in the posterior fossa, diagnosed as ETMR, which subsequently underwent treatment‐induced maturation. Prior to chemotherapy, histopathology revealed an abundance of highly proliferative, undifferentiated cells and multilayered rosette structures. Conversely, post‐treatment histopathology revealed cell populations that differentiated into neuronal and ganglionic phenotypes. At 5‐year follow‐up, the patient remains progression‐free.ConclusionThis finding contributes to the few reports to date of post‐treatment differentiation/maturation of ETMR cell populations, with an implication for less cytotoxic therapeutic interventions aimed at differentiation.