Abstract Paraneoplastic syndromes affecting the nervous system are unique among immune-mediated disorders in that the trigger of the immune response is known: tumor expression of proteins normally restricted to neurons (or other immunoprivileged sites, such as testis) but ectopically expressed in some cancers results in an immunological response characterized by high titers of antibodies targeting the “onconeuronal” antigen. A T-cell response is also elicited in some paraneoplastic syndromes and may be the cause of neuronal destruction. In some instances genes that code for the antigens recognized by the autoantibodies have been identified, cloned and sequenced. Some of the proteins so identified are RNA binding proteins but their specific function has not been identified. In some individuals with cancer but no paraneoplastic syndrome, low titers of antibody can be identified in the serum. Low titers of antibody are associated with a better prognosis of the cancer. Experimental animals immunized against a paraneoplastic antigen are partially protected against tumors that express that antigen.