Background: Tuberous sclerosis is an autosomal dominant condition characterized by the development of benign neoplasms of the brain, kidney, and skin. Progressive growth and malignant transformation of brain and kidney lesions constitute the major cause of morbidity and mortality in adults with tuberous sclerosis. In addition, growth of skin lesions may be disfiguring to patients. Objective: The purpose of this study was to determine whether benign tumors in patients with tuberous sclerosis are angiogenic. Methods: Brain, kidney, and skin tumors from patients with tuberous sclerosis were stained with CD31, a specific marker of vascular endothelium. In addition, we used Northern blot analysis to demonstrate that renal angiomyolipoma cells express the potent angiogenesis stimulator vascular endothelial growth factor (VEGF). Results: Brain, kidney, and skin neoplasms from patients with tuberous sclerosis are highly angiogenic. Renal angiomyolipoma cells produce the potent angiogenic factor VEGF. Conclusion: Benign neoplasms of patients with tuberous sclerosis are highly vascular. Our results provide a rationale for antiangiogenic therapy in the treatment and prevention of tuberous sclerosis-associated neoplasms. (J Am Acad Dermatol 2002;46:376-80.)