The primary focus of this chapter is on the gross and microscopic pathology of retinoblastoma. Epidemiology, genetics, clinical features and the differential diagnosis are discussed by other authors. Retinoblastoma has an encephaloid appearance grossly and can exhibit endophytic, exophytic, indeterminate and diffuse infiltrative growth patterns. Histopathologically, tumors are composed of basophilic areas of viable tumor, which typically form perivascular cuffs and sleeves, and eosinophilic areas of necrotic cells that frequently contain foci of reddish-purple calcification. Increasing degrees of retinal differentiation noted histopathologically include Homer Wright rosettes, Flexner-Wintersteiner rosettes and fleurettes or photoreceptor differentiation. High-risk histopathologic features include massive choroidal invasion, retrolaminar optic nerve invasion, extraocular extension and anterior segment involvement.