text: Cryoglobulins Identification classification and novel biomarkers of mysterious proteins Cryoglobulins consist of serum immunoglobulins that precipitate below 37 C and resolubilize upon warming The clinical triad of cryoglobulinemia usually includes purpura weakness and arthralgia Cryoglobulinemic syndrome clinically defined as a systemic vasculitis is associated with chronic infection with hepatitis C virus HCV and autoimmune disorders and can evolve into B cell malignancies While the current literature about HCV associated cryoglobulinemia is not very limited little is known about the immunologic and serologic profiles of affected patients Therefore comprehension of the pathogenetic mechanisms underlying cryoprecipitation could be very helpful Due to the persistence of viral antigenic stimulation biomarkers to use after the worsening progression of HCV infection to lymphoproliferative and or autoimmune diseases are widely needed Laboratory methods used to detect and characterize low concentrations of cryoprecipitates and immunotyping patterns could improve patient management The most critical factor affecting cryoglobulin testing is that the pre analytical phase is not fully completed at 37 C 