UNLABELLED: The presence of recurrent medullary thyroid carcinoma (MTC) can be detected early by measurement of serum calcitonin levels, but the localization of recurrent tumors is often difficult. METHODS: We compared 99mTc-sestamibi scans with computed tomographic (CT) scans in 10 patients with recurrent MTC, who had basal serum calcitonin values ranging from 220-61800 ng/liter. Two patients additionally had bone scans performed because of the clinical suspicion of bone metastases. RESULTS: Seven of the 10 patients had at least one site of abnormal 99mTc-sestamibi uptake, and all of these patients had basal serum calcitonin values > 6000 ng/liter. Only five of the 10 patients had abnormal CT scans. Technetium-99m-sestamibi scans detected 22 abnormal sites in the soft tissues of the neck and chest, while CT scans detected only 11 lesions in the neck and chest. Five of these sestamibi positive sites (in the neck and mediastinum of one patient) were confirmed histologically to represent MTC. When imaging the liver, CT scans detected 47 lesions in three patients while 99mTc-sestamibi scans detected none. One of these liver lesions was confirmed as MTC histologically. When imaging bone in two of the patients, the bone scans detected 17 abnormal sites, while 99mTc-sestamibi scans detected six abnormal sites. CONCLUSION: Technetium-99m-sestamibi scans complement CT and bone scans in the localization of recurrent MTC in patients with extremely high calcitonin levels. Technetium-99m-sestamibi scans are more sensitive than CT scans in the assessment of the soft tissues of the neck and chest, but CT is more appropriate for imaging hepatic lesions and bone scans are better for imaging bone lesions. Technetium-99m-sestamibi scans are unlikely to be abnormal in patients with only mild elevation of calcitonin.