The objective of this study was to investigate the predictive value of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting malignant transformation of plexiform neurofibromas in children with neurofibromatosis type 1 (NF1). An electronic search of the medical records was performed to determine patients with NF1 who had undergone FDG-PET for plexiform neurofibroma between 2000 and 2011. All clinical, radiologic, pathology information and operative reports were reviewed. Relationship between histologic diagnosis, radiologic features and FDG-PET maximum standardized uptake value (SUV(max)) was evaluated. This study was approved by the Institutional Review Board of our institution. 1,450 individual patients were evaluated in our Multidisciplinary Neurofibromatosis Program, of whom 35 patients underwent FDG-PET for suspected MPNST based on change or progression of clinical symptoms, or MRI findings suggesting increased tumor size. Twenty patients had concurrent pathologic specimens from biopsy/excision of 27 distinct lesions (mean age 14.9 years). Pathologic interpretation of these specimens revealed plexiform and atypical plexiform neurofibromas (n = 8 each), low grade MPNST (n = 2), intermediate grade MPNST (n = 4), high grade MPNST (n = 2), GIST (n = 1) and non-ossifying fibroma (n = 1). SUV(max) of plexiform neurofibromas (including typical and atypical) was significantly different from MPNST (2.49 (SD = 1.50) vs. 7.63 (SD = 2.96), p < 0.001). A cutoff SUV(max) value of 4.0 had high sensitivity and specificity of 1.0 and 0.94 to distinguish between PN and MPNST. FDG-PET can be helpful in predicting malignant transformation in children with plexiform neurofibromas and determining the need for biopsy and/or surgical resection.