We compared the effectiveness of epithelial membrane antigen (EMA) with 2 newly described markers, X-linked inhibitor of apoptosis protein (XIAP) and an isoform of glucose transporter (GLUT-1), in the distinction between malignant mesothelioma (MM) and benign effusion (BE) in body cavity fluids. Immunohistochemical studies were performed on cell block sections from 35 cases of histologically confirmed MM and 38 BEs, using antibodies to EMA, XIAP, GLUT-1 (GLUT-1m, monoclonal; GLUT-1p, polyclonal). Results were graded based on the percentage of cells staining: negative (0%), 1+ (<25%), 2+ (25%-49%), 3+ (50%-74%), and 4+ (75%-100%). The performance of each marker was compared using receiver operating characteristic curve analysis. EMA demonstrated the best accuracy, with an area under the curve of 0.91 as compared with XIAP (0.67), GLUT-1m (0.74), and GLUT-1p (0.80). Based on these findings, EMA is a better marker than XIAP or GLUT-1 for the diagnosis of MM.