The detection of radioiodine (I-131)-negative metastases of differentiated thyroid carcinoma (DTC) has been hitherto successfully tried by the well-known synthetic somatostatin analogue indium-111-labeled DTPA-octreotide (In-111 pentetreotide). The objective of this study was to evaluate the usefulness of scintiscan with the newer synthetic somatostatin analogue Tc-99m depreotide, in the restaging of papillary thyroid carcinoma (PTC) with detectable serum thyroglobulin (Tg) levels and negative I-131 whole-body scan (WBS). Whole-body planar and cervico-thoracic tomographic scintigraphy (single-photon emission tomography-SPET) with Tc-99m depreotide was performed in a 68-year-old male patient suffering from PTC stage III, with a mild increase in serum Tg levels coupled with a recent negative I-131 WBS. The findings were compared with those of neck ultrasonography (US) and computerized tomography (CT). Nodal neck dissection and histopathology provided the definitive diagnosis. Tc-99m depreotide scanning revealed foci of cervical lymph node metastases, which did not accumulate I-131. The findings were in accordance with neck US and CT. Histopathology established the diagnosis of metastatic cervical lymph node PTC. Lymph node immunoreactivity was positive for the somatostatin receptor subtypes 2, 5 and 3. Scintigraphy with Tc-99m depreotide could prove a useful adjunct to the armamentarium for the follow-up of PTC, especially in the setting of detectable serum Tg and negative I-131 WBS. ' 2006 Wiley-Liss, Inc.Key words: papillary thyroid carcinoma; metastasis; Tc-99m depreotide; I-131 whole-body scan Thyroid carcinoma (TC) is diagnosed in about 20,000 individuals in Europe each year and leads to 1,500-2,000 deaths annually. 1 It is the most frequent malignancy of the endocrine glands. However, well-differentiated TC (DTC) is a rare disease, accounting for less than 1% of all malignant neoplasms in humans. 2 The highest incidence rates are reported in countries with normal or even high dietary iodine status. The papillary subtype of DTC (PTC) comprises 60-70% of all thyroid malignancies, with a female-tomale ratio of 3:1. [2][3][4] In keeping with the literature, regional recurrence after total thyroidectomy ranges between 5 and 20% of the cases, while distant metastases develop in less than 10% and mainly involve the lungs and bones. 1 Lymph node metastases range from 35% to more than 70% in different series and are associated with higher rates of tumor recurrence. According to the 2002 TNM classification, their location, size, number and extension beyond the node capsule probably exert a prognostic impact. 1 However, recurrent PTC does not usually cause early symptoms; hence, prompt laboratory and imaging diagnostic accuracy is of the utmost importance.The determination of serum thyroglobulin (Tg) level has an established significant role in the follow-up and therapeutic decision-making of PTC after total thyroidectomy and thyroid remnant ablation with radioiodine (I-131); its detection indicates thyroid remnant, r...