Sixteen unequivocal, diffuse malignant mesotheliomas ( DMM ) of pleura and eight diffuse pleural tumors simulating DMM , all from autopsied cases, were studied with hematoxylin and eosin, mucicarmine, diastase-periodic acid-Schiff ( DPAS ), colloidal iron, carcinoembryonic antigen, and keratin immunoperoxidase stains. Collagen production by tumor cells when identifiable was diagnostic of DMM and was found not only in sarcomatous and "biphasic" mesotheliomas but also focally in "epithelial" variants. In "epithelial" areas, a constant nuclear/cytoplasmic (N/C) ratio with variable cell size often imparted a distinctive appearance of regularity, and mucin-negative DPAS -negative vacuoles or ground-glass cytoplasmic zones always could be found. Most metastatic carcinomas featured a high N/C ratio; some but not all had mucicarmine-positive or DPAS -positive vacuoles. Stains for carcinoembryonic antigen and keratin did not discriminate between DMM and metastatic carcinoma. Distant metastases were present in 12 of the 16 DMM cases but were clinically occult in 11 cases.