We report the case of a 15-year-old female with a medulloepithelioma who underwent enucleation following plaque brachytherapy. To our knowledge, this is the first report of the histopathological findings of medulloepithelioma following brachytherapy. Histopathology revealed radiation-related changes such as hyalinized vessels, photoreceptor atrophy, degenerative changes of the retina, and preretinal fibrous tissue. Additionally, the retinal nerve fiber layer showed signs of cystoid edema. Subretinal fluid, not commonly associated with medulloepithelioma, was also noted on histology; interestingly, it was seen adjacent to the tumor on B scan prior to brachytherapy. After enucleation, hyaline cartilage was also present on histology, although neuroepithelium was absent. Although we do not have pathological confirmation that neuroepithelium was present prior to brachytherapy, it is possible that brachytherapy preferentially affected neuroepithelium, leading to decrease in tumor size.