Lucio's phenomenon (LPh) is a vasculitis clinically described in 1852 and microscopically documented in 1948 in patients with diffuse lepromatous leprosy; however, at present, there is no a clear concept about the pathogenesis of the necrosis, or about the type, size, and site of the damaged vessel. The objective of this study was to elucidate the type, size, site, and form of vessel damage in LPh in a retrospective, clinical, and histopathological study. Clinical information was obtained from the charts and records and/or from the histopathology request. Slides stained with hematoxylin and eosin, Ziehl-Neelsen, and Fite-Faraco were retrieved from our files. Direct immunofluorescence had been performed in 6 cases. Twelve cases fulfilled clinical evidence to make unequivocal diagnosis of diffuse lepromatous leprosy with LPh. All of them had necrotic, irregular, purpuric, and/or ulcerative lesions, which under the microscope showed medium-sized arteries, with their walls involved by clusters of macrophages containing large amounts of bacilli, distortion of the structure of the vessel wall, narrowing, and obliteration of their lumen. Smaller vessels showed changes of the leukocytoclastic type. LPh is a distinctive type of granulomatous and necrotizing panvasculitis; the involved vessels are mostly medium-sized arteries, located deeply in the skin, at the base, and within the hypodermis, but any other vessel is likewise involved, their occlusion leads to ischemic necrosis of the whole skin, frequently with detachment of the epidermis. These changes explain clearly and logically the clinical features observed more than 150 years ago.