The aim of this study was to assess the usefulness of contrast perfusion echocardiography in the differential diagnosis of different types of cardiac masses. Conventional echocardiography and contrast perfusion echocardiography were performed in 72 patients with cardiac masses. The degree of contrast enhancement of the mass and an adjacent section of myocardium after injection of contrast agent was determined by visual inspection and quantitative time-signal intensity curve analysis. The difference in maximal steady-state pixel intensity between the mass and the adjacent myocardium (Delta A(mass-myocardium)) was calculated. All masses had a pathologic diagnosis or resolved after anticoagulation. All 16 cardiac masses without enhancement on visual inspection were confirmed to be cardiac thrombi. Twenty-four masses with incomplete enhancement on visual inspection were recognized as benign tumors with validation methods. Of the 32 cardiac masses with complete enhancement, 30 were confirmed as malignant tumors and two as benign tumors with validation methods. The sensitivity and specificity of Delta A(mass-myocardium) in differentiating thrombi from tumors were 93% and 100%, respectively, and 100% and 97% in differentiating malignant tumors from benign tumors and thrombi. Both visual and quantitative assessment of degree of enhancement of cardiac masses in relation to the adjacent myocardium during contrast perfusion echocardiography had high diagnostic accuracy for differentiation of a thrombus from a tumor or a benign tumor from a malignant tumor. (C) 2015 World Federation for Ultrasound in Medicine & Biology.