PURPOSE Differentiation of incidental adrenal lesions remains a challenge in diagnostic imaging, especially on single-phase portal venous computed tomography (CT) in the oncological setting. The aim of the study was to explore the ability of dual-energy CT (DECT)-based iodine quantification and virtual non-contrast (VNC) imaging and advanced radiomic analysis of DECT for differentiation of adrenal adenomas from metastases. METHODS A total of 46 patients with 49 adrenal lesions underwent clinically indicated staging DECT and magnetic resonance imaging. Median values of quantitative parameters such as VNC, fat frac- tion, and iodine density in DECT images were collected and compared between adenomas and metastases using non-parametric tests. Magnetic resonance imaging, washout CT, and clinical follow-up were used as a reference standard. Diagnostic accuracy was assessed by calculat- ing receiver operating characteristics. A DECT tumor analysis prototype software was used for semiautomatic segmentation of adrenal lesions and extraction of radiomic features. A radiomics prototype was used to analyze the data with multiple logistic regression and random forest clas- sification to determine the area under the curve (AUC). RESULTS The study cohort (60.87% women; mean age: 66.91 ± 12.93 years) consisted of 32 adenomas and 17 metastases. DECT-based VNC imaging (AUC=0.89) and fat quantification (AUC=0.86) differentiate between adrenal adenomas and metastases with high diagnostic accuracy (P < .001). Analysis of radiomic features revealed that DECT features such as VNC imaging and fat fraction (AUC = 0.87-0.89; < .001) and radiomic features such as 90th percentile and total energy (AUC = 0.88-0.93; P < .001) differentiate with high diagnostic accuracy between adrenal adeno- mas and metastases. Random forest classification revealed an AUC of 0.83 for separating adrenal adenomas from metastases. CONCLUSION Virtual non-contrast imaging and fat quantification as well as extraction of radiomic features accurately differentiate between adrenal adenomas and metastases on single-phase oncologic staging DECT.