Cryoglobulinemia is a clinical condition characterised by the presence of circulating globulins that precipitate at a temperature lower than 37 degrees Celsius and re-dissolve with warming. We can distinguish 3 different types of cryoglobulinemia, according to their immunochemical characteristics. Cryoglobulinemia can be associated with infectious, inflammatory or neoplastic disease. Cryoglobulinemia type II can be associated with chronic HCV-hepatitis. Clinically, cryoglobulinemias cause hyperviscosity-related symptoms or lesions by immunocomplex deposition (cryoglobulinemic vasculitis). Many organs and systems can be involved, from the skin to the joints, from the central nervous system to the kidney. Diagnosis requires a careful clinical and physical evaluation and the demonstration of circulating cryoglobulins by cryoprecipitation and immunoelectrophoresis. The therapeutic goals are the treatment of the underlying diseases and the complication and prevention of progression/relapse. It is obvious that this disorder can involve different specialists, but the internist plays a central role: he identifies the disease and the associated condition, he treats the underlying disorder and refers the patient to the specialists for the organ-specific manifestations.