PURPOSE: To assess the utility of 2-[18F] fluoro-2-deoxy-D-glucose (FDG) PET in differentiating malignant and benign diffuse pleural disease, and to compare it with CT. MATERIALS AND METHODS: Both FDG PET and CT scans were performed in 20 consecutive patients with diffuse pleural disease (13 malignant and seven benign cases). In FDG PET, peak standardized uptake value (SUV) as well as visual assessment of abnormally increased uptake in the pleura was evaluated. The results were compared with CT findings. RESULTS: With only visual assessment of PET images, sensitivity, specificity, and accuracy for malignancy were 92%, 43%, and 75%, respectively. With peak SUV of 4.8 or more, the corresponding figures were 100%, 57%, and 85%, respectively, and on CT interpretation, were100%, 57%, and 85%, respectively. Tuberculous empyema simulated malignant pleural disease both on FDG PET (3/6 patients with peak SUV more than 4.8) and CT (3/6 patients). CONCLUSION: For the differentiation of malignant and benign diffuse pleural disease, FDG PET and CT are equally accurate. Combined visual and quantitative assessments of PET images enhance discriminatory ability. Tuberculous empyema simulates malignant pleural disease both on FDG PET and CT.