Uterine tumors with neuroectodermal differentiation, frequently referred to as primitive neuroectodermal tumors (PNETs), are uncommon. The clinicopathologic features of 17 such cases reviewed at the M.D. Anderson Cancer Center (MDACC) are presented along with a review of the literature. All of the pathology material was reviewed at MDACC, and in all cases, immunohistochemistry contributed to the diagnosis. In 12 cases, in situ hybridization techniques were used to determine whether a rearrangement of the EWSR1 gene, required for a diagnosis of peripheral PNET, was present. Clinical information was obtained from a patient chart review. Ages ranged from 31 to 81 years (median 58). Clinical presentations included vaginal bleeding (9), back pain (1), presumed fibroids (2), pelvic mass (1), incidental finding at hysterectomy (1), and unknown (3). Twelve patients had surgery or imaging to determine stage: I (2), II (0), III (6), and IV (4). Five patients had biopsy only. Ten tumors had only neuroectodermal components. In 7 tumors, the neuroectodermal component was admixed with an additional component including unclassified sarcoma (2 cases), rhabdomyosarcoma, endometrioid carcinoma, adenosarcoma and malignant mixed Mullerian tumor (2 cases). Follow-up, available for 13 patients, ranged from 2 to 41 months with 7 patients dead of disease 2 to 26 months after diagnosis. Six patients are alive with no evidence of disease after follow-up ranging from 6 to 41 months. Four patients were lost to follow-up. Results for the most commonly used immunohistochemistry studies include cytokeratin, 13/15 tumors negative (2 focally positive); synaptophysin, 15/16 tumors positive; neurofilament, 10/11 tumors positive; and CD99, 7/9 tumors positive (2 tumors had nonspecific cytoplasmic staining). None of the 12 tumors tested had a detectable rearrangement in the EWSR1 gene. Uterine tumors with neuroectodermal differentiation, similar to more common endometrial malignancies, tend to occur in postmenopausal women and frequently present with vaginal bleeding. An immunohistochemistry panel including cytokeratin, neurofilament, synaptophysin, and CD99 can highlight neuroectodermal differentiation and identify tumors for which molecular testing should be considered. Tumors without a rearrangement of the EWSR1 gene should be descriptively characterized as uterine tumors with neuroectodermal differentiation or alternatively central type PNETs rather than PNET, not otherwise specified to avoid confusion with peripheral PNET.