There is compelling circumstantial evidence that humoral autoimmune response may be involved in the generation of paraneoplastic neurologic syndromes (PNS). However, still it is unproven whether the autoantibody is pathogenic or represents an epiphenomenon to the actual disease process. Paraneoplastic antibodies have been identified in patients with PNS which react with similar antigenic epitopes in tumor and neurons. However, the antigens identified by the paraneoplastic antibodies are primarily intracellular in location, questioning the pathogenetic role of the antibody. The molecular events of antigen processing and presentation, T-cell receptor restriction, polyclonal B-cell proliferation, cellular immunity, and the role of cytokines in mediation of neuronal injury must be further defined in order to elucidate the role of autoimmunity in the pathogenesis of these disorders.