Mature cystic teratomas have been widely studied relative to their tissue components derived from all 3 embryonic layers, and immunohistochemical methods have demonstrated a variety of neurohormonal polypeptides. To our knowledge, Langerhans cells (LCs), which are a peculiar component of epidermis, have not been reported in ovarian teratomas. The origin of these cells is still a matter of debate, ranging from bone marrow stem cells to neural elements. Thirty mature teratomas of the ovary were studied by immunohistochemistry using CD1 (specific against dendritic LCs), S100 protein (against LCs and melanocytes), and melan-A and HMB45 (against melanocytes). Furthermore, antibodies for identifying subsets of lymphocytes and monocytes (CD3, CD4, CD8, CD20, and CD68) were used. Histologic examination showed teratomas with the presence of all 3 embryonic layers in variable proportions in 23 cases, while 7 teratomas were composed only of epidermis without appendages or other tissues. Immunohistochemistry identified LCs among the suprabasal layers of epidermis in the same sites at which melanocytes were seen in the basal layer. CD1-positive LCs sometimes appeared to cross the basal membrane and penetrate the subepidermal tissue (related to their known migratory ability), and they were associated there with T-cell line lymphocytes (CD3 positive). These findings were commonly observed in teratomas that included all 3 embryonic layers and neural tissues. Notably, LCs and melanocytes were undetectable in the 7 teratomas composed of epidermis only. Our observations of LCs in ovarian teratomas led us to consider these cells to be derived from neural cells, possibly related to Schwann cells, in accord with the original description by Langerhans. In fact, LCs are always associated with melanocytes, which are universally considered to be derived from the neural crest, as are Schwann cells and peripheral nerves. Finally, we propose that LCs may be part of a cytoimmunologic system related to the T-cell compartment, with a stem cell derived from the neural crest.