The p53 gene is altered in up to 60 % of most types of human cancer arising from a wide spectrum of tissues. This leads to abnormal p53 protein accumulation inside the cancer cell. Some patients with an abnormal p53 function develop in a yet unclear mechanism an immunresponse against p53 protein. p53 autoantibodies gain increasing attention since several studies (1-14) described their detection in sera from patients with various malignancies (e.g., colorectal, ovarian, oral, head&neck, trophoplastic and lung carcinomas). The presence of p53 autoantibodies seems to be associated with more progressive cancers and reduced disease-free survival of (surgically) treated patients. There is accumulating evidence that p53 autoantibodies may be indicative for a poor prognosis and a higher risk of tumor relapse. p53 autoantibodies have a useful potential in patient monitoring during therapeutical follow-up. A postoperative significant drop in p53 autoantibodies may be the result of complete tumor resection and successful (adjuvant) chemotherapy. The percentage of positive sera for cancer patients varied over a wide range, which might be due to different diagnostic accuracy of several tests described by Rohayem et al. in (15). Among three tests used, the STZ ELISA (STZ für Angewandte Biologische Chemie) showed the highest diagnostic accuracy with a significant difference from other tests (15). In early stages of a progressive malignancy like colorectal cancer established tumor markers (for example,CEA, carcinoembryonic antigen) are of low sensitivity. Detection of CEA is not linked to the p53 immune response, so p53 autoantibodies evaluation supplies the clinician with additional data. The combination of p53 autoantibodies and tumor marker CEA significantly increases sensitivity of monitoring colorectal cancer patients (16). Due to high specificity (100%), the monitoring of p53 autoantibodies after surgery and adjuvant chemotherapy of colorectal cancer patients has potential for early diagnosis of tumor relapse (1). Likewise, Takeda et al. (12) noticed a significant correlation between curability of colorectal cancer by surgical tumor resection and postoperative disappearance of p53 autoantibodies in these patients. Zalcman and co-workers (11) could demonstrate that a rapid, specific decrease of the p53 autoantibodies titer was correlated with successful chemotherapy of lung cancer patients. Detection of p53 autoantibodies has a high potential for the differential diagnosis of gestational trophoblastic tumors (GTTs) and their serial measurements are clinically useful to monitor disease progression and to assess response to therapy in GTTs (2). In some malignancies like pancreatic and prostatic carcinomas, leukemias or melanoma, p53 autoantibodies are less frequent and of minor clinical value (3,5). It must be stressed that p53 autoantibodies are not specific for any particular cancer. However, as these antibodies are only rarely found in patients with non-malignant disorders (see below) or healthy blood donors, their specificity is higher than that of many other tumor markers.