BACKGROUND: Diffuse uveal melanocytic proliferation is a rare paraneoplastic syndrome resulting in rapid bilateral visual loss due to proliferation of benign melanocytes within the choroid and ciliary body. Most of the previously reported cases have been seen with bilateral involvement and typical ocular features. PATIENT: The authors report the case of a 61-year-old man who presented with uniocular posterior pole lesions at the level of the retinal pigment epithelium and subsequently developed the typical bilateral lesions of diffuse uveal melanocytic proliferation. His clinical course was typical, with visual disturbance preceding signs and symptoms of malignancy by 5 months. Rapid decline ensued, and he eventually died 10 months after the onset of visual symptoms. RESULTS: Results of ocular pathologic examination showed the typical choroidal thickening due to the proliferation of melanocytes and the primary tumor was found to be an undifferentiated adenocarcinoma originating in either the pancreas or the esophagus. CONCLUSIONS: The very early funduscopic and fluorescein angiographic findings of diffuse uveal melanocytic proliferation are presented as well as the evolution, ocular pathology, and possible mechanisms for its development.