The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments. Tregs dysfunction has been observed in patients with paraneoplastic syndromes and/or with autoimmune diseases, while the increase of Tregs has been associated with poor cancer patients prognosis. Novel therapies have employed antibodies against Tregs immune-checkpoint receptors with the aim to boost immune response in cancer patients. The presence of autoantibodies to tumors antigens has also been investigated as a marker for cancer detection and cancer patients prognosis. This report reviews the current knowledge on the analysis and meaning of autoantibodies to self antigens detected in cancer and autoimmune disease patients.