An electron microscopic study of 4 solitary schwannomas and 2 neurofibromas of peripheral nerves was performed with the aim of investigating the debated histogenesis of the two types of lesion. Our observations confirm that solitary schwannoma is composed almost exclusively of cells with characteristics of differentiated Schwann cells, thus providing evidence for a neuroectodermal origin of the tumor. Analysis of the ultrastructure of neurofibroma shows the presence of 3 different types of cells: Schwann-like cells, perineurial-like cells, and fibroblast-like cells. Perineurial-like cells were prevalent in our observations. These findings as well as the many controversial aspects of the origin of neurofibroma could be explained by separating this type of neoplasia into two pathological forms: perineurial and interstitial. Moreover, the numerous differences between solitary schwannoma and neurofibroma allow us to hypothesize a different cellular origin for each tumor. If confirmed by further observations, this would explain the difference in the capacity of the two types of neoplasia to undergo malignant change, an occurrence almost unknown in solitary schwannoma yet relatively common in neurofibroma.