Warfarin-induced skin necrosis is a rare complication of anticoagulant treatment. The incidence of this complication is undetermined, but it has been estimated to occur between 1:100 and 1:10,000 of patients treated with anticoagulants. Coumarin skin necrosis occurs almost exclusively in patients with venous thrombosis between the 3rd and 10th day after beginning anticoagulation. Although protein C deficiency is the most common underlying hypercoagulable state reportedly associated with warfarin skin necrosis, very few cases have been linked to congenital protein S deficiency. This article addresses the association of hereditary protein S deficiency and warfarin skin necrosis, and provides suggestions for management.