Retinoblastoma (RB) is the most common intraocular tumor in children. It arises from the nuclear layer of the retina, with different growth patterns: endophytic, exophytic, and mixed. Retinoblastoma also has characteristic histopathological appearance with areas of viable tumor, necrosis, and calcifications. The tumor differentiation can be determined by the presence of rosettes-Flexner-Wintersteiner rosettes as well as fleurettes-and tends to become less differentiated with age. Histopathological risk factors are used as prognostic indicators and will be discussed in this chapter together with the typical tissue diagnostic features. These will include optic nerve/choroidal invasion, extraocular extension, and anterior segment involvement. Other prognostic factors with less impact will be discussed as well including the amount of necrosis, mitotic figures, and grading of anaplasia. Furthermore, we will briefly discuss different regression patterns and posttreatment findings in enucleated globes.

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