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AIM To investigate the value of CT spectral imaging in differentiating adrenocortical carcinoma (ACC) and pheochromocytoma (PCC). METHOD 17 patients underwent dual phase contrast enhanced CT with spectral CT mode, including 12ACCs and 5 PCCs followed by surgery. Monochromatic images at 70keV were reconstructed. Iodine concentrations in the lesions were normalized to those of the aorta. The normalized iodine concentrations (NIC) and the lesion-normal parenchyma iodine concentration ratio (LNR), Spectrum Curve Slope (K) were calculated. The student t-test was performed to compare quantitative parameters. Two readers qualitatively assessed lesion types on the basis of imaging features. Sensitivity and specificity were compared between the qualitative and quantitative studies. RESULTS NICs and LNRs, K, CT values during the VP, and NICs during the AP in patients with ACC differed significantly from those in patients with PCC: mean NICs were 0.52±0.09 mg/ml vs 0.74±0.18 mg/ml, respectively, during the VP. Mean LNRs were 0.03±0.02 vs 0.01±0.01, respectively, during the VP. Mean Ks were 1.69±0.30 vs2.70±0.89, respectively, during the VP. Mean CT values were 65.17±4.16HU vs 93.15±8.94HU, respectively, during the VP. Mean NICs during AP were 0.31±0.02 mg/ml vs 0.20±0.15 mg/ml, respectively. The NICs for ACC were higher than those of PCC during both AP and VP. The LNRs, Ks, CT values for ACC were lower than those of PCC during the VP. The differences were significant (p < 0.05). CONCLUSION The adrenocortical carcinoma and pheochromocytoma have distinct characteristic findings on CT spectral imaging. CT spectral imaging may help the differential diagnosis of adrenocortical carcinoma and pheochromocytoma. CLINICAL RELEVANCE/APPLICATION CT spectral imaging may help the differential diagnosis of adrenocortical carcinoma from pheochromocytoma preoperatively.