Cold labile serum and plasma proteins can cause a variety of clinicopathological symptoms. Due to altered physicochemical properties, cryoglobulins and cryofibrinogens may cause increased serum viscosity, cold dependent protein precipitation or, in rare cases, serum gelification. Cold agglutinins, on the other hand, cause temperature dependent agglutination of erythrocytes and eventually hemolysis. All pathological cold dependent serum and plasma phenomena are associated with either neoplasma, autoimmune disorders, various infections or are considered as "essential". While the diagnosis of these conditions remained largely unchanged during the last 10 years, new aspects regarding etiology, pathogenesis, and therapy have arisen.