BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a hereditary tumour predisposition syndrome with a frequency of 1:3000. Patients are prone to develop tumours of the central and peripheral nervous system. Around 10% develop malignant peripheral nerve sheath tumours (MPNST) mostly arising from plexiform neurofibroma (PN) with 15% of MPNST arising in children and adolescents. 18F-FDG-PET is a sensitive method in differentiating PN and MPNST. METHODS: This retrospective analysis included 39 NF-1 patients with plexiform neurofibroma that underwent 18F-FDG-PET or PET/CT screening for malignant transformation. Mean age at first PET was 13.5 years (2.6 - 22.7), m:f = 18:21. 91 examinations were performed in these patients. Image data were reanalysed and linked to clinical data. 6 patients (7 lesions) had symptoms suspicious for malignant transformation (rapid growth n = 5, pain n = 1, functional deficit n = 1), whereas 33 patients were asymptomatic. RESULTS: All malignant tumours could be identified by 18F-FDG-PET imaging, in both symptomatic and asymptomatic patients. All lesions judged as benign by 18F-FDG imaging were either histologically benign if removed or remained clinically silent during follow up. All malignant lesions had a SUVmax >3.14. We detected malignant lesions with a sensitivity of 100% and a specificity of 77.6% but with a low positive predictive value ppV of 23%. DISCUSSION: Malignant transformation of PN also occurs in asymptomatic children. Detection of MPNST at early stages could increase the possibility of oncologically curative resections and reduce neurological dysfunction. This may drastically improve survival rates in NF-1 patients at high risk for MPNST formation. The high risk and dismal prognosis of MPNST in patients with NF-1 has to be balanced against the use of a weak radioactive tracer in a tumour predisposition syndrome with a relatively low ppV.