Differential diagnosis between mixed cryoglobulinemia and other autoimmune-lymphoproliferative disorders in the setting of HCV infection. Mixed cryoglobulinemia (MC) syndrome, primary Sjögren's syndrome (pSS), and rheumatoid arthritis (RA) show a clinico-pathological overlap, including the possible association with HCV infection. The following parameters may be usefully employed for a correct differential classification/diagnosis: pSS shows typical histopathological pattern of salivary gland involvement and specific autoantibodies (anti-RoSSA/LaSSB), which are rarely found in MC patients; conversely, cutaneous leukocytoclastic vasculitis, visceral organ involvement (glomerulonephritis, hepatitis), low C4, and HCV infection, are typically found in MC. Moreover, erosive symmetrical polyarthritis and serum anti-cyclic citrullinated peptide antibodies (anti-CCP) characterize classical RA. Finally, B-cell non-Hodgkin's lymphoma (B-NHL) may complicate these diseases, more frequently MC and SS. The appearance of B-NHL can be timely suspected by careful clinico-serological monitoring and diagnosed by bone marrow/lymph node biopsies and total body CT scan. RF: rheumatoid factor. (modified from . Ferri C and Mascia MT, Curr Opin Rheumatol 2006, 18: 54–63, with permission from Lippincott Williams & Wilkins).