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. We identified all patients with pathologically proven subependymomas presenting to our institution between 1998 and 2016. We retrospectively reviewed clinical, radiographic, histologic, and surgical outcomes data in all patients who underwent surgical resection. Immunohistochemical analyses for cell lineage markers were performed. A total of 31 patients with pathologically proven subependymomas were identified. Of these, 7 asymptomatic lesions were discovered at autopsy and 24 symptomatic cases were treated surgically. There were 15 (48%) lateral ventricle tumors, 11 (35%) fourth ventricular tumors, and 5 (17%) spinal tumors. Symptomatic intracranial lesions most commonly presented with headaches and balance and gait abnormalities. Subependymomas had no distinguishing radiographic features that provided definitive preoperative diagnosis. At last follow-up, no patient treated surgically experienced recurrence. Immunohistochemical analyses demonstrated a diffusely GFAP-positive glial neoplasm with mixed populations of cells that were variably positive for Olig2, NHERF1, Sox2, and CD44. The Ki67 proliferation index was generally low (<1% in many of the tumors). Subependymomas demonstrate mixed populations of cells expressing glial lineage markers as well as putative stem cell markers, suggesting these tumors may arise from multipotent glial progenitors that reside in the subventricular zone. Definitive diagnosis requires surgical sampling. Although the clinical course of subependymomas appears benign, the inability to radiographically diagnose these lesions, and the possibility of an alternative malignant lesion support a low threshold for early and safe maximal resection.