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BACKGROUND 99mTc sestamibi scanning and aspiration biopsy can predict the histopathological result of a thyroid nodule fairly accurately. OBJECTIVE To determine the accuracy of 99mTc sestamibi scanning in detecting malignancy in patients with thyroid nodule confirmed by definitive histopathological report after thyroidectomy. MATERIAL AND METHODS A total of 69 patients with a solitary thyroid nodule were studied. In all patients, fine needle aspiration, total thyroidectomy for suspected thyroid cancer, and histological analysis of the surgical specimen were performed. There were 54 patients with a positive 99mTc sestamibi scan; of these, malignancy was confirmed by histological analysis in 25 and excluded in 29. There were 15 patients with a negative 99mTc sestamibi scan; of these, three had a final diagnosis of cancer and 12 were confirmed as cancer-free. RESULTS The diagnostic accuracy of 99mTc sestamibi scanning in detecting malignancy in thyroid nodules was determined through a statistical analysis. 99mTc sestamibi scan for thyroid cancer had a sensitivity of 89.28% and a specificity of 29.25%. The positive predictive value was 46.29% and the negative predictive value was 80%. CONCLUSIONS We believe that 99mTc sestamibi scan should be routinely used in all patients with a thyroid nodule and an indeterminate result on fine needle aspiration. This procedure is most useful in excluding malignancy in patients with a negative 99mTc sestamibi scan.