The authors describe an infant girl who, at 10 months of age, presented with a large right parietooccipital tumor causing increased intracranial pressure, mass effect, and midline shift. The tumor was completely resected, and the entirety of the histology was consistent with glioblastoma. She was subsequently placed on adjuvant high-dose chemotherapy consisting of carboplatin, vincristine, and temozolomide, according to Head Start III, Regimen C. Three months after the complete resection, tumor recurrence was noted on MR imaging, during the third cycle of chemotherapy, and biopsy revealed malignant astrocytoma. Given the recurrence and the patient's intolerance to chemotherapy, a palliative course was pursued. Unexpectedly, the patient was alive and had made significant developmental improvements 18 months into palliation. Subsequently, however, signs of increased intracranial pressure developed and imaging demonstrated a very large new tumor growth at the site of prior resection. The recurrence was again fully resected, but microscopy surprisingly revealed pleomorphic xanthoastrocytoma throughout. The clinicopathological and genetic features of this girl's unusual neoplasm are detailed and potential pathogenic hypotheses are explored in this report.