This study analyzed the impact of prognostic variables of age, sex, histopathological diagnosis, extent of disease at diagnosis, and surgical intervention on well differentiated thyroid carcinoma and how surgical treatment, radioactive iodine, and radiotherapy influence the patients' outcomes. There have been 1599 patients with well differentiated thyroid cancer treated and followed at the University of Texas M.D. Anderson Cancer Center from 1948 to 1989. The median follow-up for all patients was 11.0 yr, with the maximum follow-up being 43 yr and the minimum follow-up being 1 yr. The patients were predominantly female (2.3:1), with papillary (81%) and intrathyroidal carcinomas (42%) at the time of diagnosis. Sixty-six percent of the patients had a total thyroidectomy, 7% received external radiotherapy, and 46% had radioactive iodine as part of the treatment of the original disease; the overall recurrence rate was 23%, and the death rate was 11%. This study showed that treatment with radioactive iodine was the single most powerful prognostic indicator for increased disease-free interval (P less than 0.001) and that its use significantly increased survival as well. No benefit was obtained from treatment with external radiotherapy. Children had the best overall survival, but of the adult patients, females who had intrathyroidal papillary disease treated with total thyroidectomy, who had been given radioactive iodine, and whose disease had been diagnosed between 20-59 yr of age had the best prognosis.