Previous studies of the intraoperative use of a hand-held gamma probe to localize metastases and primary tumors of colorectal cancer have shown improved assessment of tumor spread and changes in surgical management based on added information gained by radioimmunoguided surgery. Following the injection of 180 MBq [111In-DTPA-D-Phe1]-pentetreotide and/or 500 MBq 99mTc-dimercaptosuccinic acid (both for dual-radionuclide scintigraphy) preoperative somatostatin receptor imaging [11 patients with GEP tumors] and dual-radionuclide scintigraphy. (8 patients with relapsing medullary thyroid carcinomas) was performed. One patient with a metastasizing pheochromocytoma underwent 123]-MIBg scintigraphy. Results were combined with the information obtained from conventional imaging modalities. Intraoperative radiodetection was performed 24 hours after administration of [111In-DTPA-D-Phe1]-pentetreotide or 4 hours following the injection of 99mTc(V)DMSA using a hand-held gamma probe (Tec Probe 2000. Stratec, FRG). Intraoperative gamma counting localized 39 somatostatin receptor positive lesions of GEP tumors whereas preoperative receptor imaging visualized 81%, surgical palpation 41% and radiological imaging modalities localized only 31%. In 8 patients with recurrent medullary thyroid carcinoma the surgeon was successful in localizing and removing 18 tumor lesions by the help of the gamma probe. Dual-radionuclide scintigraphy revealed 77% (Octreoscan 5/18; 99mTc-V-DMSA 9/18), surgical palpation 55% and conventional imaging methods (CT, sonography) only 38% of all lesions detected intraoperatively by the hand-held gamma probe. In summary, this preliminary data show that intraoperative hand-held gamma probe detection of microscopic and occult endocrine tumors is feasible and more sensitive than external scintigraphy and conventional imaging.