Hemolytic disease by cold-reacting antibodies is a rare form of hemolytic anemia. In most cases a subjacent cause is found. This disease is generally related with reactive lymphoproliferative processes (infections by the Epstein-Barr virus and cytomegalovirus) or uncontrolled lymphoproliferative disorders (lymphomas, Waldenström disease, chronic lymphatic leukemia). The presence of high titers of cryoagglutinins have recently been described in patients infected by the human immunodeficiency virus (HIV); however, clinical manifestation as hemolytic anemia is very rare. A 37 year old male diagnosed with infection by HIV, non Hodgkin's lymphoma of Burkitt type non convoluted cells, chronic hepatopathy by the B and C virus, Brouet type III cryoglobulinemia and hemolytic anemia by cold-reacting antibodies is herewith described. This multiple association is exceptional as is the important clinical repercussion of the hemolytic anemia derived from the high titers and above all the wide thermic interval of the cryoagglutinin present. Finally, the relation of cryoagglutinin with each of these entities, the concomitant presence of cryoglobulins and the evolution of the titers of the same with the chemotherapy treatment administered for the lymphoma is analyzed.