Skin and soft tissue necrosis, in association with the coumarin derivatives, characteristically afflicts females between the third and tenth days of treatment. Anatomic regions abundant in subcutaneous fat are most commonly affected. Many of these patients have underlying serious medical problems. Three additional patients with tissue infarction complicating coumadin therapy are presented. Possible etiologic mechanisms are discussed, but the basic physiopathologic condition remains an enigma. Venous thrombosis can be a related clinical phenomenon. Treatment perspectives are outlined.