A novel prognostic staging classification encompassing all forms of thyroid carcinoma was created for the National Thyroid Cancer Treatment Cooperative Study (NTCTCS) Registry, with the goal of prospective validation and comparison with other available staging classifications. Patient information was recorded prospectively from 14 institutions. Clinicopathologic staging was based on patient age at diagnosis, tumor histology, tumor size, intrathyroidal multifocality, extraglandular invasion, metastases, and tumor differentiation. Between 1987 and 1995, 1607 patients were registered. Approximately 43% of patients were classified as NTCTCS Stage I, 24% Stage II, 24% Stage III, and 9% Stage IV. Patients with follicular carcinoma were more likely to have "high risk" Stage III or IV disease than those with papillary carcinoma. Of 1562 patients for whom censored follow-up was available (median follow-up, 40 months), 78 died of thyroid carcinoma or complications of its treatment. Five-year product-limit patient disease specific survival was 99.8% for Stage I, 100% for Stage II, 91.9% for Stage III, and 48.9% for Stage IV (P < 0.0001). The frequency of remaining disease free also declined significantly with increasing stage (94.3% for Stage I, 93.1%for Stage II, 77.8% for Stage III, and 24.6% for Stage IV). The same patients also were staged applying six previously published classifications as appropriate for their tumor type. The predictive value of the NTCTCS Registry staging classification consistently was among the highest for disease specific mortality and for remaining disease free, regardless of the tumor type. The NTCTCS Registry staging classification provides a prospectively validated scheme for predicting short term prognosis for patients with thyroid carcinoma.