Splenic infarct is a rare condition often related to haematological, cardiovascular, autoimmune or infectious diseases diagnosed with increasing frequency due to the large use of abdominal imaging techniques. Cryoglobulins are serum proteins that reversibly precipitate at low temperatures, small vessels vasculitis represent their most common clinical manifestation and are often associated with chronic liver disorders or with lymphoproliferative diseases. Here the authors report the cases of two patients, both affected by chronic liver disease associated with cryoglobulinemia, admitted to our unit for an on-going active infectious disease (without signs of endocarditis) who presented multiple splenic infarcts as an unexpected complication. The authors hypotize that in both cases splenic infarct may be related not only to a thrombogenic state or to splenic vasculitis but also to other immuno-mediate mechanism related to cryoglobulins synthesis and clearance.