Abstract CASE REPORT A 5-year-old girl diagnosed with a posterior fossa standard-risk medulloblastoma underwent surgery followed by proton therapy (PT) 23.4 Gy(RBE) (1.8 Gy(RBE)/fr) to the craniospinal axis plus a boost of 30.6 Gy(RBE) (1.8 Gy(RBE)/fr) to the tumor bed and maintenance chemotherapy according to HIT-SIOP PNET 4 protocol. The patient remained disease-free for 4 years after the end of treatmen. MRI showed a new left temporo-occipital lesion 8x10x10 mm which was irradiated from cranial field during the craniospinal phase but outside of the boost area, consistent with inoperable recurrence. She was then re-irradiated with a second course of PT 50.4 Gy(RBE) (1.8 Gy(RBE)/fr) and subsequently started on temozolomide. Periodic MRI scans showed progressive reduction of the lesion for 10 months, when new lesion progression occurred within the re-irradiated fieled. Considering the stable clinical conditions of the patient, the minimal size of the lesion, and the uncertain nature between actinic damage or cancer, a watchful waiting approach was adopted. Few months later, the area increased. [18F]FET-PET/CT evaluation documented an uptake of the drug compatible with metabolically active lesion. A biopsy was performed, and histology showed a CNS sarcoma. Genetical testing excluded cancer predisposition syndromes. Chemotherapy with bevacizumab and irinotecan was started, but the MRI showed significant progression of the disease and the patient died 6 months after the diagnosis. CONCLUSION MRI is the main diagnostic method in the follow up of CNS neoplasms, but it has limitations in discriminating recurrences/secondary tumours and tissue changes due to previous treatments, particularly radiotherapy. Recently, the use of [18F]FET-PET/CT is being investigated, but literature is still poor in children and most cases refer to high-grade gliomas. It is desirable to study it further, as it may play a relevant role in differentiating equivocal cases, as in our patient.