A 4-year, 9-month-old boy had a history of leukocoria of the right eye for approximately six months prior to admission. The other eye was normal. There was no family history of retinoblastoma. Funduscopy disclosed a large white mass extending from the nasal pars plana to the mid-pupillary zone and the posterior pole with a near total retinal detachment in the superior temporal quadrant. A B-scan ultrasound showed an echo dense area of the anterior portion of the mass. A CT scan showed intraocular tissue densities with no evidence of optic nerve involvement or extraocular extension. Immunohistochemistry of a fresh frozen portion of tumor revealed reactivity with antibodies directed against interphotoreceptor retinoid-binding-protein (IRBP), neuron-specific enolase, glial fibrillary acidic protein, S-antigen, focal reactivity with opsin, and scattered cytoplasmic staining for cyclic GMP and cyclic GMP phosphodiesterase. Biochemical analysis of fresh frozen tissue samples confirmed the presence of IRBP. Transmission electron microscopy disclosed occasional Flexner-Wintersteiner rosettes connected by zonula adherens-like junctions. These showed inner segment-like structures containing prominent mitochondria, portions of cilia and fragments of outer segment material. These data, along with the immunocytochemistry indicates a predominant neuronal nature of the tumor cells with significant photoreceptor-like differentiation.