Peginterferon is now the gold standard of therapy in patients with chronic hepatitis C virus infection. Extrahepatic manifestations of HCV are usually treated with interferon alfa. Here we report on a patient with HCV-related cirrhosis and cryoglobulinaemia who presented with an acute and long-lasting exacerbation of vasculitis during treatment with peginterferon. To our knowledge this is the first report of an acute exacerbation of cryoglobulinaemia-related vasculitis involving skin, peripheral nerve and kidney in a patient treated with peginterferon for HCV-related cirrhosis. The long half-life of peginterferon might explain the long-lasting symptoms of vasculitis. Clinicians should be aware of possible sustained flare of cryoglobulinaemia-associated vasculitis in patients receiving peginterferon.