Angioedema due to an acquired deficiency in the inhibitor of the first component of human complement (CI-INH) is a rare syndrome that is usually identified as acquired angioedema (AAE). The clinical features of C1-INH deficiency, which may also be of genetic origin (hereditary angioedema, HAE), include subcutaneous, non-pruritic swelling, involvement of the upper respiratory tract, and abdominal pain due to partial obstruction of the gastrointestinal tract. Unlike those with HAE, AAE patients have no family history of angioedema and are characterised by the late onset of symptoms and various responses to treatment due to the hypercatabolism of C1-INH. The reduction in C1-INH function leads to activation of the classical complement pathway and complement consumption, as well as activation of the contact system leading to the generation of the vasoactive peptide bradykinin, increased vascular permeability, and angioedema. AAE is frequently associated with lymphoproliferative diseases ranging from monoclonal gammopathies of uncertain significance (MGUS) to non-Hodgkin's lymphoma (NHL) and/or anti-C1-INH inactivating autoantibodies. The coexistence of true B cell malignancy, non-malignant B cell proliferation and pathogenic autoimmune responses suggests that AAE patients are all affected by altered B cell proliferation control although their clinical evolution may vary.