In the imaging of the mediastinum, benign lesions mimicking malignancy constitute potential pitfalls in interpretation. Localization and characteristic imaging features are key to narrow the differential diagnosis and avoid potential pitfalls in interpretation. Based on certain anatomic landmarks, the mediastinal compartment model enables accurate localization. Depending on the anatomic origin, mediastinal lesions can have various etiologies. The anatomic location and structures contained within each mediastinal compartment are helpful in generating the differential diagnoses. These structures include thyroid, thymus, parathyroid, lymph nodes, pericardium, embryogenic remnants, and parts of the enteric tracts, vessels, and nerves. Imaging characteristics on computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET/CT), including attenuation (fluid, fat, calcification), contrast enhancement, and metabolic activity, aid in narrowing the differential diagnoses. Understanding the roles and limitations of various imaging modalities is helpful in the evaluation of mediastinal masses. In this review, we present potential pitfalls in the imaging of mediastinal lesions with emphasis on the mimics of malignancy.