The authors report on a case of a 7-year-old girl who was found on routine preschool screening at age 4 years to have unilateral decreased vision and a retinal lesion consistent clinically with the retinoma or retinocytoma variant of "spontaneously regressed retinoblastoma." The patient was followed closely with photographic documentation. After remaining stable for 3 years, her tumor grew rapidly and seeded the vitreous, prompting enucleation. Histopathologic examination disclosed that the newer elevated part of the tumor was an undifferentiated retinoblastoma, whereas the base of the tumor had the characteristic benign histopathologic features of retinoma/retinocytoma including bland nuclei, a fibrillar eosinophilic stroma, scattered fleurettes, calcific foci within viable tumor, and no mitoses. Immunohistochemical stains disclosed that immunoreactivity for retinal S antigen, S-100 protein, and glial fibrillary acidic protein was confined to cells in the differentiated basal part of the tumor. These histopathologic observations support the concept that tumors with the clinical characteristics of the patient's original lesion are benign variants of retinoblastoma that have arisen de novo rather than retinoblastomas that have undergone spontaneous regression. The clinical developments in this case suggest that retinomas or retinocytomas rarely undergo malignant transformation after a period of clinical dormancy and underscore the necessity for close follow-up of patients with presumed regressed retinoblastoma.