Cryofibrinogenemia is due to the presence of reversibly cold-precipitating plasma proteins and material, consisting mostly of fibrinogen, fibronectin, and fibrin. This condition can be idiopathic or secondary to infection, thromboembolic states, neoplasm, or connective tissue disease. The characteristic lesions of cryofibrinogenemia include purpura and ulcerations. Histologically, the lesions of cryofibrinogenemia demonstrate fibrin thrombi within vessels, with no evidence of vasculitis. Treatment of cryofibrinogenemia should be directed at the underlying disease process, if one can be found. Other treatments have included the anabolic steroid stanozolol, which is presently unavailable, anticoagulants, immunosuppressive agents, plasmapheresis, and the combination of streptokinase and streptodornase. We report a case of a 61-year-old male smoker with a 10-year history of intermittent ulcerations of both legs and feet. Two separate biopsies showed epidermal ulceration and thrombi within superficial dermal vessels without evidence of vasculitis. These findings, together with the presence of elevated plasma cryofibrinogen, led to the diagnosis of cryofibrinogenemia. The patient continued to have ulcerations despite efforts to control his high blood pressure, cold avoidance, local wound care, and treatment with pentoxifylline 800 mg three times daily. However, when colchicine 0.6 mg twice daily was added to the patient’s care, this led to rapid healing of his ulcerations. He has remained ulcer free for 2 years taking the combination of colchicine and high-dose pentoxifylline. Efforts to reduce the dose of these agents have repeatedly led to recurrences, and remission has promptly followed re-establishment of the combination. To our knowledge, this is the first report documenting use of the combination of colchicine and high-dose pentoxifylline to successfully treat ulcers due to cryofibrinogenemia.