Cryoglobulins are proteins that can undergo reversible precipitation from the serum upon cooling to a temperature lower than 37 °C. These proteins are composed of immunoglobulins with or without a mixture of complement proteins. Wintrobe and Buell first described this cryoprecipitation phenomenon in 1933 in a patient with multiple myeloma who presented with hyperviscosity-related symptoms (Wintrobe MM, Buell MV. Bull Johns Hopkins Hosp 52:156–165, 1933). It was Lerner and Watson who coined the term “cryoglobulin” in 1947 (Lerner AB, Watson CJ. Am J Med Sci 214:410–415, 1947). Strictly, the term “cryoglobulinemia” refers to the presence of cryoglobulins in serum. However, it is commonly used to refer to a syndrome whose symptoms are a consequence of these cryoglobulins. This condition was first described by Meltzer and Franklin in 29 patients with serum cryoglobulins and a common pattern of symptoms that comprised of purpura, arthralgias, and weakness in the presence of elevated rheumatoid factor and end-organ dysfunction such as neuropathy and renal disease (Meltzer M, Franklin EC. Am J Med 40:828–836, 1966).