Neoplastic angioendotheliomatosis (NAE) is a rare, fatal disease characterized by widespread intravascular proliferations of malignant cells of putative endothelial origin. Clinically, dermatologic and bizarre neurological manifestations predominate, but review of the reported cases of NAE reveals ophthalmic involvement to be frequent. To our knowledge, no reports of NAE have appeared in the ophthalmic literature. We describe three cases of NAE with the ocular manifestations of visual loss, cells in the vitreous, retinal artery occlusion, retinal vascular and pigment epithelial alterations, nystagmus, and cortical blindness. Autopsies (including eyes and central nervous system) revealed pancorporal involvement by intravascular anaplastic cells in each patient. In two patients massive extravascular involvement was also present. The tumor cells lacked ultrastructural features of endothelial cells and failed to stain for factor-VIII-related antigen. Common leukocyte antigen, a maker for hematopoietic cells, particularly lymphocytes, was detected on tumor cells in all cases, indicating that NAE is probably an extranodal lymphoma. The dramatic response of the central nervous system lesions to radiotherapy in one case supports this contention. It is suggested that this disorder be treated as a malignant lymphoma.