OBJECTIVE: Subependymomas are infrequent, low-grade gliomas associated with the ventricular system and the spinal cord. Little is known about the origin and natural history of these slow-growing lesions. METHODS: We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2013. We retrospectively reviewed clinical, radiographic, histological, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for a number of cell lineage markers was performed. RESULTS: A total of 24 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 17 symptomatic cases were treated surgically. There were 8 lateral ventricle tumors, 5 spinal tumors and 4 fourth ventricular tumors. Symptomatic intracranial lesions most commonly presented with headaches, changes in vision, and balance difficulty. Subependymomas had no distinguishing radiographic features that provided definitive pre-operative diagnosis. At last follow up, no patient treated surgically experienced recurrence, although one patient with histologically mixed subependymoma-ependymoma subsequently developed and was treated for a remote glioblastoma. Immunohistochemical analyses demonstrated mixed populations of cells that were variably positive for Olig2, NeuN, Sox2, and CD44. CONCLUSION: Subependymomas demonstrate a mixed population of cells expressing neuronal and glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotential progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. While the clinical course is usually benign following surgical resection, the rare association with glial malignancy and the potential for malignant progression merits further investigation.