SummaryAim: To retrospectively analyse the expression of somatostatin receptor subtypes 2 (SSTR 2) and 5 (SSTR 5) in thyroid malignancies, possibly the most relevant subtypes for targeted therapy with somatostatin peptide radioligands. In addition, findings were also correlated with the course of disease. Patients, methods: 87 consecutive patients (59 women, 28 men) with thyroid malignancy were included; 52 had papillary carcinoma, 24 follicular carcinoma, six medullary carcinoma, two poorly differentiated carcinoma and three anaplastic carcinoma. After initial therapy 70 (80.5%) patients showed complete remission, 11 (12.6%) patients partial remission with clinical and biochemical signs of residual disease and six (6.9%) patients progressive disease. The immunohistochemi- cal staining results of the primary malignancy for SSTR 2 and SSTR 5 were semiquanti- tatively assessed and correlated with various outcome parameters. Results: In 10 of 87 (11.49%) thyroid cancer samples SSTR 2 showed positive immunohistochemical expression as compared to 75 of 87 (86.20%) for SSTR 5. All SSTR 2-positive cases expressed SSTR 5. Persistent or recurrent disease was found in 17 of 87 cases (19.54%). Fifty percent (6 /12) of SSTR 5-negative patients showed persistent disease as compared to 14.7 % (11 / 75) of SSTR 5-positive patients: seven of these were exclusively SSTR 5-posi- tive, 4 showed dual expression of SSTR 5 and SSTR 2 (p = 0.01). No case showed only SSTR 2 expression. Conclusions: SSTR 5 was shown to be the main receptor subtype in the analysed differentiated or anaplastic thyroid malignancies, whereas SSTR 2 was found only in a small percentage. Deficient SSTR expression may indicate higher risk for persistent or recurrent disease after initial therapy. For this reason immunohistochemistry can be considered a prognostic marker which should be further validated in prospective studies.