The immune system confines neoplasia at various stages of tumor development. Whereas the role of cellular immunity has been investigated widely and utilized in the clinic, the importance of humoral immunity in this process has begun to emerge only in recent years. Circulating antinuclear autoantibodies (ANAs) typically found in autoimmune conditions, have also been detected in cancer patients and in healthy elderly individuals. The pathogenic role of ANAs in autoimmunity is well studied; however, little research has been carried out to elucidate the functions of ANAs in cancer patients. Experimental data favoring the antitumor activity of ANAs might support the clinical testing of monoclonal ANAs as a cancer therapy, if confirmed by further experiments.