OBJECTIVE: To reexamine the age, metastases, extent, and size (AMES) risk criteria for well-differentiated thyroid cancer with the effect of therapy on outcome. DESIGN: Review of patient medical records and direct-contact follow-up. SETTING: Two tertiary referral centers. MAIN OUTCOME MEASURES: Recurrence or death. PATIENTS: One thousand nineteen patients with well-differentiated thyroid cancer treated between 1940 and 1990. RESULTS: One thousand nineteen patients with well-differentiated thyroid cancer were treated between 1940 and 1990, with a mean follow-up of 13 years, including a recent group of 264 patients treated from 1980 to 1990 at 2 different institutions with a mean follow-up of 8 years. The AMES criteria were used to designate high- and low-risk patients. The entire group had 229 high- and 790 low-risk patients; the percentage of high-risk patients decreased slightly after 1960. From 1940 to 1960, 1960 to 1979, and 1980 to 1990, the high-risk groups had survival rates of 48%, 62%, and 47%, respectively. For the low-risk patients, survival rates were 96%, 98%, and 98%, respectively. Recurrences occurred in 5% of low-risk patients and were usually curable; in high-risk patients, recurrence was associated with a 75% mortality. In low-risk patients, there was no significant difference in recurrence or death according to type of operation (unilateral or bilateral) or use of radioactive iodine. In high-risk patients, there were trends toward but no significant improvement in survival with bilateral surgery and radioactive iodine therapy; thyroid replacement was associated with a significant improvement in survival. CONCLUSIONS: The AMES risk criteria remain highly valid predictors of risk. They define most low-risk patients for whom radical treatment may add excess morbidity but not improve already excellent prognoses.