<p>Retroperitoneal diseases encompass a broad and heterogeneous spectrum, ranging from benign conditions to aggressive malignancies. Clinical presentation is often nonspecific, and physical examination is limited by the deep location of the retroperitoneum. Consequently, cross-sectional imaging—primarily computed tomography (CT) and magnetic resonance imaging (MRI)—is central to detection, characterization, and staging, playing a key role in guiding management and surgical planning. Imaging evaluation is challenging due to overlapping appearances, difficulty determining the site of origin and extent of disease in large or infiltrative processes, and the complex, incompletely understood retroperitoneal anatomy. A structured, anatomy-based interpretive framework fosters improved diagnostic accuracy. Initial assessment focuses on localization and lesion composition. Distinguishing between pathology arising from retroperitoneal organs and primary retroperitoneal processes, combined with characterization of composition (e.g., solid, cystic/fluid, fat, calcification, gas, or mixed), allows generation of a focused differential diagnosis. Integration of key imaging and clinical features then refines and prioritizes diagnostic considerations. Common pitfalls in interpretation are related to technique, mischaracterization of lesion location or composition, and underestimation of disease extent. Recognition of these potential sources of error, coupled with a systematic approach to image interpretation, can improve diagnostic accuracy and better inform clinical decision-making in retroperitoneal pathology.</p>