Previous studies have concluded that lymph node metastases do not affect survival rates in patients with differentiated thyroid carcinoma and, therefore, nodal metastasis has not been evaluated as a prognostic factor in recent definitions of risk groups. To determine the significance of nodal disease, we reviewed 227 consecutive patients with differentiated thyroid carcinoma (173 with papillary, 37 with follicular, and 17 with Hürthle cell carcinoma). Of 70 (31%) patients with lymph node metastases (14 [20%] palpable preoperatively and 56 [80%] detected by routine sampling of middle and lower cervical nodes), 13 (19%) developed a recurrence compared with only 3 of 157 (2%) without nodal disease (p less than 0.01). Sixty-eight patients were treated with modified neck dissection, 63 of whom received adjuvant radioiodine. There were 10 recurrences in 63 patients (16%) who had been treated with radioiodine, compared with 3 recurrences in 7 (42%) patients who did not receive adjuvant radioiodine. Follow-up ranged from 2 to 28 years, with a mean of 8 years. Involvement of the lymph nodes was a marker for systemic disease occurring synchronously in 4 of 5 patients who presented with distant metastases and preceding systemic recurrence in 9 of 10 patients. Four patients (2%), all with lymph node metastases (three with concomitant extrathyroidal invasion and one with systemic metastases at initial presentation), died of thyroid carcinoma. Cervical lymph node metastases were associated with a higher incidence of recurrence and occurred synchronously or preceded the development of distant metastases in 13 of 15 (87%) patients. Although these findings were not statistically significant for overall survival, they lend support to routine cervical lymph node sampling for detection of and modified neck dissection with adjuvant radioiodine therapy for treatment of lymph node metastases. Such measures should reduce the subsequent recurrence rate and permit early detection and treatment of systemic disease.