Necrosis of skin and soft tissue as a complication of oral anticoagulation therapy is a rare condition with approximately 200 cases documented in the world. Coumadin-induced skin necrosis is a painful skin lesion, sudden, localized, initially erythematous or hemorrhagic, that becomes bullous and eventually culminates in gangrenous necrosis. It develops mainly in women around 50 years of age who are usually obese and have been treated for thrombophlebitis or pulmonary embolism. There seems to be a marked predilection for areas with increased subcutaneous fat content, such as breasts, thighs, and buttocks. The injury is so significant that plastic surgery is frequently required to repair the damaged tissue. The authors present four clinical cases of Coumadin necrosis, observed in two different institutions, and perform a literature review on the mechanisms that trigger the development of the disease. This condition still remains a diagnostic-therapeutic challenge.