Three cutaneous tumors showing massively thickened nerve fascicles, with a myxomatous matrix in a diffuse tumor mass, were studied by light and electron microscopy, immunohistochemically, and with3H-thymidine autoradiography. Corresponding to plexiforme neurofibroma, these tumors were called plexiforme neurofibroma of the skin and are compared with nerve sheath myxoma (i.e., cutaneous lobular neuromyxoma, bizarre cutaneous neurofibroma, neurothekoma, and others). In the tumors, a high proportion of perineurial cells (30%) could be detected. Compared with results from regenerating nerves, organized traumatic neuroma, and other types of neurofibroma, these findings show that all constituents of normal peripheral nerves, especially Schwann cells and perineurial cells, may be involved in the growth of peripheral nerve sheath tumors. Furthermore, autoradiography demonstrated a high proliferative activity in one of the tumors. The possible clinical relevance of this finding and the question of whether these tumors may bear a higher risk for malignancy will be discussed.