In one case, the external examination found a large, brown, firm plaque with peripheral erythema, erosions, and blisters on the back and right flank, along with fine yellowish papules in the intertriginous areas. A skin biopsy on one of the lesions revealed fragmented and clumped, irregular basophilic fibers on routine hematoxylin-eosin histopathologic examination. This finding was consistent with a diagnosis of pseydoxanthoma elasticum (PXE), a genetic disorder that carries significant morbidity and mortality. In the second case, external examination revealed large necrotic stellate ulcerations on the bilateral flanks. A skin biopsy on the periphery of the ulcer revealed calcification and thrombi within the vessels of the dermis, consistent with calciphylaxis, which is a casculopathy that develops most often in patients with renal insufficiency. Death may occur within a few months and is usually due to sepsis or visceral involvement. In the third case, the biopsy of brown papules observed on the skin revealed epidermal hyperplasia with anastomosing rete pegs and keratin-filled pseudocysts, consistent with seborrheic keratoses. This finding, combined with the history of a brain tumor 6-months prior, was consistent with the sign of Leser-Trelat. The fourth case involved skin manifestations that led to a diagnosis of scleromyxedema, which can be associated with cardiac and pulmonary complications. In all these cases, analysis of skin findings at autopsy led to the confirmation of a serious genetic disease and notification of the family, explanation for sudden death in a young person, association of skin findings with internal malignancy, and the opportunity to better understand the pathogenesis of a poorly understood disease process. 6 figures and 8 references