The tumor suppressor p53 is of particular interest in tumor diagnosis. Alterations in the p53 gene are detected in approximately 60% of the major human tumor types originating from various tissues. The most frequent forms of p53 gene alterations are point-missense mutations. This leads to a pathological accumulation of the p53 protein in tumor cells. Some patients with impaired p53 function develop an immune response by an unclear mechanism. The presence of p53 autoantibodies in the serum of cancer patients correlates with immunohistochemical staining of p53 tumor tissue. The presence of autoantibodies to p53 in serum is an indirect result of a point missense mutation in the p53 gene and is independent of the exact position of the mutation in the p53 gene. Many studies have described the detection of antibodies to the p53 protein in the serum of patients with various cancers. Alterations in the p53 gene can be detected at a very early stage of oncogenesis. It has been shown that p53 autoantibodies are detected in patients with hepatocellular carcinoma regardless of AFP level. Autoantibodies to p53 can also be detected in asymptomatic patients. Autoantibodies to p53 are an independent diagnostic marker. Their presence is associated with a more aggressive tumor type and a shortened recurrence-free life span of patients. Thus, antibodies to p53 are associated with a poor prognosis. This marker is highly specific. Patients with autoimmune pathology are an exception. In some cases, autoantibodies to p53 are detected in acute pancreatitis. Determination of autoantibodies to p53 may be important in the monitoring of cancer patients. They are significantly more frequently found in the serum of patients with relapses after surgery. Patients with malignant tumors have changes in autoantibody titers to p53 which correlate with the progression or regression of the disease. Thus, it is possible to monitor the level of autoantibodies to p53 during the course of the disease and during therapy.