Development of malignant peripheral nerve sheath tumors (MPNSTs) is a recognized complication in patients with neurofibromatosis type 1 (NF1). Differentiating benign from malignant lesions can be a difficult clinical problem. Positron emission tomography (PET) is an established method for making this differentiation with a high degree of sensitivity and specificity. There are several reports showing that fluorine-18 fluorodeoxyglucose (FDG) PET is an effective imaging modality for detecting malignant transformation with a sensitivity nearing 100%. There are very few reports of false-negative 18F-FDG PET in a patient with an MPNST. This case report describes a woman with NF1 and a grade 3 MPNST and a negative PET scan. Identification of malignant transformation in NF is a significant clinical challenge. It is important to recognize the potential limitations of 18F-FDG PET in these patients.