Mixed cryoglobulinemia (MC) are immune complexes that can deposit in small and medium size arteries and cause systemic vasculitis called cryoglobulinemic vasculitis (CryoVas). CryoVas most common clinical manifestations include purpura, arthralgia and/or arthritis, skin ulcers, peripheral neuropathy, nephritis, and may progress to more life-threatening illness. Hepatitis C virus (HCV) infection is the more frequent condition to be assessed in patients with MC, followed by connective tissue diseases and B-cell non-Hodgkin’s lymphoma. In HCV-related cases, the mainstay of CryoVas treatment is interferon free antiviral therapy. However, a significant proportion of patients who show HCV eradication will develop persistent CryoVas needing treatment intensification.