The authors describe two clinical cases of cryoglobulinemia. A 70 years old woman, having skin ulcers on lower limbs, arthralgias, paresthesias and constitutional symptoms, for about 10 months. Exams revealed mild anemia, elevation of the biological parameters of inflammation and aminotransferases, positive cryoglobulin and rheumatoid factor in serum, and a severe reduction in C4 complement fraction. Hepatitis C virus (HCV) serology was negative. Idiopathic mixed cryoglobulinemia was diagnosed and corticosteroid therapy started. Given the lack of response, cyclophosphamide and plasmapheresis were added. Two weeks later the patient died in septic shock. The second case refers to a 41 years old female, with untreated hepatitis C who developed over a 6 month period petechiae and livedoid lesions on the lower limbs, peripheral neuropathy, and constitutional symptoms and was admitted with intestinal necrosis. Exams were consistent with the diagnosis of mixed cryoglobulinemia associated, with HCV. She started therapy with ribavirin and pegylated interferon-alpha, with improvement.