OBJECTIVE To quantitatively assess the imaging characteristics of thyroid nodules in dual-energy computed tomography (CT) imaging for differentiation of benign and malignant lesions. METHODS Dual-energy CT imaging was performed on 97 surgically removed thyroid nodule specimens prior to their pathologic examination. Iodine- and water-based material decomposition images and 101 sets of pseudomonochromatic images of each thyroid specimen were reconstructed for quantitative imaging analysis. The iodine concentration and effective atomic number (Zeff) of thyroid nodules and surrounding normal thyroid tissues, HU curve slope (λHU), and mean CT values of nodules were compared between different pathologic categories. RESULTS In the 97 specimens, a total of 169 nodules were confirmed pathologically, including 108 nodular goiters (group A), 47 follicular adenomas (group B), and 14 papillary carcinomas (group C). Statistical analysis showed a significant difference between benign (A and B) and malignant (C) groups in iodine concentration (P < 0.001), λHU (P < 0.001), and Zeff (P < 0.001). For mean CT values, there existed statistical difference between groups A and C, but no difference between groups B and C. No statistical significance was found at iodine concentrations, the Zeff, or λHU in thyroid tissues surrounding nodules (P > 0.10). Additionally, water content was constant and homogeneous in nodules and adjacent thyroid tissues (P > 0.10). CONCLUSIONS Pseudomonochromatic imaging reconstruction and material decomposition-based quantitative dual-energy CT imaging have promising potential for diagnostic differentiation of benign and malignant thyroid nodules.