Thirty-two patients with differentiated thyroid carcinomas with distant metastasis were examined using a radioactive iodine (131I) tracer dose prior to 131I therapy and followed up for 10 years or until death (whichever occurred first). Nineteen patients who received 131I therapy had an accumulation of 131I in the metastases (group I) and 15 of those patients were alive more than 10 years after the first 131I treatment. In contrast, all 13 patients in whom the metastases did not show accumulation of 131I died within 10 years. Of the latter group, eight patients had received 131I therapy (group II), four of whom died with anaplastic changes within 5 years of treatment. p53 gene mutation was identified by immunohistochemistry in primary thyroid carcinoma tissue from patients with anaplastic changes that were evident during total thyroidectomy. Five patients did not receive 131I therapy (group III), of whom one, who also had a p53 gene mutation in the original tumor, died with anaplastic change 10 years after thyroidectomy. Seven patients in group I had p53 gene mutations in their thyroid carcinoma tissues, but none showed anaplastic changes. Our results suggest that 131I therapy may be useful for patients with distant metastases, with or without p53 gene mutations, which show accumulation of 131I from tracer and therapeutic doses. In contrast, 131I therapy is apparently not effective in patients who do not show sufficient accumulation of 131I, but rather, may cause early anaplastic changes with a p53 gene mutation.