OBJECTIVES: Cold agglutinins and cryoglobulins are uncommon in the same patient as observed in our case. CASE REPORT: A 74-year-old patient suffered repeated episodes of hemolytic anemia for one year and had hepatitis C anti-virus antibodies. Mixed cryoglobulinemia was found at levels which increased during episodes of acute hemolysis in addition to anti-I cold agglutinins. Two-dimensional electrophoresis revealed identical oligoclonal cold agglutinins and cryoglobulins. DISCUSSION: Unlike mixed cryoglobulinemia, cold agglutinins are not known to occur subsequent to hepatitis C infection. The identical immunoglobulins observed in our patient suggest a common origin. Chronic anti-I cold oligoclonal agglutinins are rarely observed and could be an intermediary step towards monoclonal lymphopathy as has been described in prolonged hepatitis C infection.