We prospectively studied 43 patients with solitary cold thyroid nodules greater than 1.5 cm in diameter to determine the comparative diagnostic value of radionuclide thyroid angiography (RTA), technetium-99m methoxyisobutylisonitrile (Tc-99m-MIBI) scintigraphy and power Doppler ultrasonography (PDUS) in the differentiation of benign and malignant thyroid nodules. Perfusion of the nodules in RTA was compared with the perfusion in the surrounding normal thyroid tissue and classified as follows: 0, avascular; 1, hypovascular; 2, isovascular; 3, hypervascular. Tc-99m-MIBI uptake in the nodules compared with that in surrounding thyroid tissue was scored for both early and delayed images as follows: 0, cold; 1, decreased; 2, equal; 3, increased. PDUS patterns were classified as nodule vascularisation patterns. The malignancy criteria were set as follows: hypervascular nodule with rapid washout in RTA; complex ring sign with anarchic structure or delta sign in PDUS, and positive retention and increased uptake in the nodule in the early and delayed Tc-99m-MIBI images. These data were compared with the histopathological results. Histology revealed thyroid carcinoma in nine patients (five cases of papillary carcinoma, three of follicular carcinoma and one of medullary carcinoma) and benign conditions in 34 patients (30 cases of nodular goitre, three of lymphocytic thyroiditis and one of follicular adenoma). Sensitivity, specificity and accuracy were, respectively, 0.89, 1.00 and 0.97 for RTA, 1.00, 0.76 and 0.81 for PDUS, and 0.67, 0.91 and 0.86 for Tc-99m-MIBI scintigraphy (when nodules with increased uptake in both the early and the delayed images and a positive retention index were considered as malignant). RTA, Tc-99m-MIBI scintigraphy and PDUS could be helpful in the preoperative assessment of solitary cold thyroid nodules. In this study, RTA was found to be the most accurate and specific method for differentiation of malignant from benign thyroid nodules.