OBJECTIVES: Somatostatin receptor scintigraphy (SRS) with (111)In-octreotide has been suggested as a potential tool for the detection of recurrent or metastatic differentiated thyroid cancer when no radioiodine uptake can be demonstrated in tumour sites. However, there is no consensus concerning the performance and clinical impact of this examination in such instances. DESIGN AND METHODS: A prospective study was undertaken to evaluate SRS in 43 patients (18 men, 25 women) with papillary (n=20), follicular (n=9), insular (n=6) and oncocytic (n=8) thyroid carcinomas with elevated serum thyroglobulin (Tg) levels and no detected radioiodine uptake. RESULTS: Evaluation criteria were interpreted in terms of an assumed presence of tumoural tissue. Sensitivity of SRS was 51%, clearly lower than that of conventional imaging procedures, and of positron emission tomography using [(18)F]-2-fluoro-2-deoxy-d-glucose, performed in a subset of 27 patients. In addition, we observed two false-positive foci of uptake of octreotide that corresponded to inflammatory pulmonary sites. The sensitivity was higher in patients with Tg levels greater than 50 microg/l (76%) for detecting mediastinal lesions (93%), and in patients with oncocytic cancer (88%). Finally, SRS changed treatment strategy in four patients. CONCLUSION: In differentiated thyroid cancer, SRS is a moderately sensitive method for the detection of lesions unable to concentrate iodine and appears useful only in patients with very high Tg levels or in oncocytic cancer.