Objective: To assess the properties of adrenal lesions with and without known primary cancer and investigate predictors for differential diagnosis between benign and malignant adrenal enlargement. Methods: This retrospective study used fluorine-18 fludeoxyglucose positron emission tomography (PET)/CT in 325 patients with adrenal lesions (229 with known primary cancer and 96 without primary cancer). Age, sex, the presence of right and left masses, nodules or hyperplasia, unenhanced attenuation, maximum standardised uptake value (SUV max ) ratio, and the presence of metastasis in other body parts and locations of the primary cancer were assessed. Univariate and multivariate analyses were used to assess variables associated with risk of adrenal metastasis. Results: Patients with adrenal metastasis vs those without had a higher frequency of primary lung cancer (52.3% vs 30.7%) but a lower frequency of gastrointestinal cancer (7.9% vs 16.6%). The frequency of other abnormalities, including adenoma and hyperplasia, was similar between patients with and without known primary cancer. A higher proportion of patients with adrenal metastasis regardless of primary cancer site were younger, had a nodule or a mass, had an unenhanced attenuation of .10 HU, had an SUV max ratio of .2.5, and had metastasis in other body parts. Analysis found independent associations of age, unenhanced attenuation of .10 HU, SUV max ratio of .2.5 and the presence of metastasis in other body parts with adrenal metastasis. The combination of the four variables was strongly associated with adrenal metastasis. Conclusion: PET/CT was useful in characterising adrenal lesions as benign or malignant and helpful in identifying adrenal metastasis and cancer severity. Advances in knowledge: PET/CT can help in the differential diagnosis between benign and malignant adrenal enlargement.The adrenal gland is a common site of metastasis in patients with cancer. Up to 50% of adrenal lesions in patients with known primary non-adrenal cancers are malignant disease [1-4]. The most common malignant lesions that metastasise to the adrenal gland include lung, liver, colon, lymphoma, melanoma, breast, kidney, oesophagus, pancreas and stomach cancer [4][5][6]. However, diagnosis of an adrenal lesion as malignant or benign can be problematic. Characterisation of these adrenal lesions is therefore critical to stage the primary disease, direct therapy and predict prognosis. Although CT and MRI are typically used to characterise a lesion, a small but important number of adrenal lesions are found to be indeterminate on crosssectional images [7][8][9].Several reports have documented the effectiveness of standalone fluorine-18 fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET) to differentiate benign from malignant adrenal lesions [8][9][10]. Interest has focused on the ability of integrated in-line PET/CT to definitively characterise these lesions given that this technique combines the anatomical and densitometrical applications of CT and the functional and metabol...