Ependymomas comprise 8 % of all intracranial tumors in children <15 years. Recent studies revealed that some supratentorial ependymomas express neuronal antigens and that high expression of neurofilament protein light polypeptide (NEFL) correlates with better clinical outcome. We retrospectively analyzed an expanded panel of proteins in 6 supratentorial, 15 posterior fossa and 4 spinal pediatric ependymomas by immunohistochemistry. Expression of high and low affinity neurotrophin receptors TrkA (NTRK1) and p75 (NGFR), pan-neuronal markers NeuN (RBFOX3) and synaptophysin, radial glial marker SOX9, adhesion molecules CD56 (NCAM) and CD44, junctional protein connexin 43 (GJA1), glial fibrillary acidic protein (GFAP), epithelial membrane antigen and proliferation associated antigen Ki-67 were evaluated in a semi-quantitative or quantitative (Ki-67 and NeuN-index) fashion. We found p75 and NeuN to be expressed at significantly higher levels in supratentorial versus infratentorial tumors and GFAP to be expressed at significantly higher levels in infratentorial lesions. In conclusion, immunohistochemical expression of p75, NeuN and GFAP differed in ependymomas depending on tumor topography supporting the view of divergent cells of origin. However, because of the small sample size the results are of preliminary nature and replication in a larger cohort would be desirable.