Malignant tumors of the retinal pigment epithelium (RPE) are exceedingly rare. We describe the histopathologic and immunohistochemical features of a RPE neoplasm that was found accidentally in a blind and painful phthisical eye.The enucleated eye was investigated by light microscopy, and tumor tissue was also studied by electron microscopy. Immunohistochemistry was performed using antibodies against HMB-45, S-100 protein, NSE, cytokeratins, vimentin, desmin, GFAP, the HNK-1 carbohydrate epitope and alpha-smooth muscle actin.The tumor was located mainly in the vitreous cavity with practically complete destruction of the retina, but foci of choroidal infiltration and extraocular extension along vascular channels were identified. The mitotic rate was high, and large areas of necrosis were present. No features of differentiation were seen, apart from occasional desmosome-like junctions and deposition of basal lamina at the ultrastructural level. Adjacent to the tumor, reactive hyperplasia and metaplasia of RPE cells was prominent. By immunohistochemistry, tumor cells revealed intense immunoreactivity with anti-vimentin and weak staining with anti-S-100 protein. The hyperplastic RPE cells also reacted for cytokeratins 8, 18 and 19 and for alpha-smooth muscle actin. At more than 1 year post enucleation the patient is well and shows no signs of recurrence or metastatic disease.We present the features of a malignant tumor of the RPE with unequivocal extraocular extension. These findings raise the possibility that RPE hyperplasia may transform into a malignant tumor.