The present study was designed to define the factors that predict survival in patients with distant metastases (DM) from papillary thyroid carcinoma. We performed a retrospective review of the records of 100 consecutive patients (45 females and 55 males; age range, 8-91 yr) who developed DM after primary treatment at our institution from, 1940-1989. Median follow-up for the 20 survivors was 21 yr (range, 3-38). Cause-specific survival rates at 5, 10, and 15 yr were 40%, 27%, and 24%, respectively, and were not significantly different between the eras 1940-1954, 1955-1969, and 1970-1989 (P = 0.74). By univariate analysis, age at diagnosis of DM was the most important predictor of survival (P < 0.0001), with improved survival occurring in younger patients. Tumor-related factors associated with improved survival included complete resection of the primary tumor (P < 0.005), histological grade 1 (P = 0.006), diploid nuclear DNA (P = 0.03), and lung as first site of DM (P = 0.018). By univariate analysis, use of radioiodine therapy was associated with improved survival (vs. other forms of therapy, P < 0.001). However, by multivariate analysis only age, site of DM, and degree of extrathyroidal invasion of the primary tumor were identified as significant predictors of survival. None of the four treatment variables (external radiation, surgery, chemotherapy, or radioiodine) was a significant predictor of survival in the Cox model. Our retrospective data indicate that 1) outcome has changed little over 5 decades for patients with DM from papillary thyroid carcinoma; and 2) current forms of therapy do not appear to impact on survival.