Cross-sectional imaging techniques allow excellent visualization of the cardiophrenic space. Under normal conditions, the cardiophrenic space is occupied by fat, the amount of which is usually increased in overweight individuals. It has been suggested that this fat accumulation correlates with the risk of cardiovascular disease. Several alterations originating above or below the diaphragm can affect the cardiophrenic space. Inflammatory lesions such as pericardial fat necrosis and tumoral masses are sometimes seen. Lymphoma is a major but not exclusive cause of cardiophrenic adenopathy and must be differentiated from lymphatic seeding of supradiaphragmatic and infradiaphragmatic malignancies. In patients with portal hypertension, cardiophrenic space varices are not uncommon. Other masses or pseudomasses occurring in this region include pericardial cysts, mediastinal tumors, and diaphragmatic hernia. Computed tomography and magnetic resonance imaging of the thorax are helpful in characterizing cardiophrenic lesions initially identified at plain radiography. Such characterization helps narrow the differential diagnosis when lesions are detected in this location. ©RSNA, 2007.