Neurofibromatosis, type 1 (NF-1) is a common genetic disorder affecting 1 in 3,500-4,000 individuals in the world. Mutations of the NF-1 gene produce a myriad of physical, medical, and psychological manifestations. Although there is a very high degree of variability in the manifestations between individuals with NF-1, the majority of children and adolescents with NF-1 encounter difficulties that negatively impact their educational attainment. NF-1 is associated with a very high incidence of cognitive deficits and learning disability, sometimes including mathematical learning disabilities (MLD). A number of possible inter-related etiologies for MLD specific to children and adolescents with NF-1 are discussed, including the high incidence of attention deficit hyperactivity disorder, visual spatial impairment, morphological and functional brain abnormalities. Thus NF-1 exemplifies the wide ranging sources of potential influences on mathematical learning and MLD. (Contains 5 figures.)