Neurofibromatosis Type 1 (NF1) is an autosomal dominant, progressive genetic disorder characterized by diverse clinical manifestations. Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas (PN), dermal neurofibromas, optic pathway tumors, brain tumors, malignant peripheral nerve sheath tumors (MPNST), juvenile myelomonocytic leukemia, and pheochromocytomas. In addition, NF1 manifests in essentially every organ system, with for example, skeletal and vascular abnormalities, and cognitive deficits. Thus, the care for individuals with NF1 requires a multidisciplinary approach. The natural history of NF1 related tumor and other manifestations is poorly understood, and for most NF1 related tumor manifestations the only standard treatment option is surgery. The NIH Clinical Center provides the ideal infrastructure for evaluation of the natural history of rare diseases. A better understanding of the natural history of NF1 related tumor and other manifestations will be helpful for the design of treatment studies. The NCI, POB has an active clinical trials program for NF1 related tumor manifestations including PN, MPNST, and in collaboration with Dr. Douglas Stewart from the NHGRI, dermal neurofibromas. Unlike individuals with refractory solid cancers, individuals with NF1 have near normal life expectancy, and their benign tumors progress more slowly than solid cancers. Individuals with NF1 may thus participate in multiple treatment trials.