Heavy chain diseases (HCDs) are monoclonal, lymphoproliferative disorders characterized by the production of incomplete heavy chains, devoid of light chains. Since the first report of gamma-HCD in 1964, alpha-HCD and mu-HCD have also been described. The clinical features of gamma-HCD may vary considerably. In contrast, alpha-HCD primarily involves the secretory IgA system and mainly the digestive tract. Its clinical pattern is strikingly uniform. alpha-HCD is the most common of the HCDs, while mu-HCD is relatively rare. The demonstration of Bence Jones proteins in the urine in association with lymphoproliferative disorders and vacuolated plasma cells in the bone marrow deserves further investigation for mu-HCD. Recently, two disease entities related to molecular abnormalities of heavy chains have been reported; heavy-chain-associated amyloidosis and heavy chain deposition disease.