The follow-up of patients with differentiated thyroid carcinoma (DTC) is traditionally carried out with (131)I whole body scan ((131)I WBS) and serum thyroglobulin (Tg) measurement. Neck ultrasonography (US) is also used. We compared the roles of Tg measurement (IRMA assay) after l-thyroxine (T4) withdrawal, (131)I WBS, and US in the diagnosis of DTC neck recurrences. Diagnosis of DTC neck recurrences was based on fine-needle aspiration biopsy (FNAB) or on histologic results. Four hundred ninety-four DTC patients (120 males, 374 females; mean age, 49.3 years), submitted to total thyroidectomy and subsequent radioablative (131)I treatment, underwent serum Tg measurement off T4 therapy, (131)I WBS, and neck US at our institution. Mean (+/- SD) follow-up time was 55.1 +/- 37.7 months. Neck DTC recurrences were detected in 51 (10.3%) patients (34 females, 17 males; mean age, 49.5 years). Neck recurrences occurred after 44.6 +/- 21.4 months from initial treatment. Serum Tg levels increased (> or = 2 ng/mL) off T4 therapy in 29 patients (sensitivity 56.8%), (131)I WBS showed neck uptake in 23 patients (sensitivity 45.1%) and coexisting distant metastases were detected in 9 of 23 patients, and US identified neck recurrence in 48 patients (sensitivity 94.1%). Of these 48 neck recurrences, 19 were found in the laterocervical compartment and 29 in the central neck compartment. Traditional techniques for the surveillance of DTC patients are not as sensitive as US in the detection of neck recurrences. Neck US detects recurrences in patients with undetectable serum Tg levels and negative IWBS and should be performed as the first-line test in the follow-up of all DTC patients. Copyright 2003 American Cancer Society.