AIM: Radioiodine is the most effective treatment modality in differentiated thyroid carcinoma, either in metastatic or residual thyroid tissue. However, sometimes dedifferentiation can develop and the effectiveness of radioactive I-131 decreases. The p53 is a tumor suppressor gene which plays an important role in controlling normal cell proliferation regulation. In the serum of healthy individuals, the presence of p53 autoantibodies is extremely rare. Mutations in this gene cause an accumulation of non-functional proteins and may lead to development of anti-p53 antibodies. The aim of the present study was to devise a simple blood test that could lead to early identification of patients with dedifferentiation. In this respect, we investigate whether the serum level of anti-p53 antibody is of diagnostic value in the follow-up of patients with high levels of thyroglobulin (Tg) and negative I-131 scan. MATERIALS AND METHODS: Patients who were diagnosed with thyroid cancer, treated with total or near total thyroidectomy and referred for I-131 therapy or low dose I-131 whole body scan were included in our study. Blood samples were taken before the administration of I-131 orally in the group of patients. Besides, 28 healthy subjects were included. We quantified the presence of p53 autoantibodies from serums. RESULTS: In the present study were enrolled 171 patients with a mean age of 47.7±13.5 years (range 16­80 years) and 28 healthy subjects with an age range of 18­52 years (mean 36.0±9.8 years). One hundred and forty-eight patients had papillary (86.5%), 7 (4.1%) follicular, 10 (5.8%) thyroid tumors of uncertain malignant potential, 2 (1.2%) Hürthle cell carcinoma, 3 (1.8%) poor differentiated, and 1 (0.6%) undifferentiated thyroid carcinoma. The p53 antibodies were positive in 16 (9.4%) patients and negative in 155 (90.6%). The p53 antibodies were positive in 3 (10.7%) healthy subjects, and negative in 25 (89.3%) healthy subjects. In five patients with high Tg level and negative radioiodine scan, who were accepted as dedifferentiated, p53 antibodies were also negative. CONCLUSION: The results of the present study suggested that the level of serum p53 antibody seems to be of limited value in the demonstration of dedifferentiation in thyroid cancer patients.