We studied 31 patients with fibrotic pleural lesions and classified them as desmoplastic malignant mesothelioma (DMM) or fibrous pleurisy (FP) using predetermined histologic criteria, including a paucicellular fibrotic pleural lesion with a storiform pattern or the "patternless pattern " of Stout, plus 1 or more of the following: invasion of chest wall or lung, bland necrosis, frankly sarcomatoid areas, and distant metastases. Staining for p53 was performed in 22 cases. Follow-up was obtained on all cases and compared with the histologic diagnoses. For 24 cases, the consensus diagnosis was DMM; 19 of these displayed frankly sarcomatoid areas, 16 showed invasion, and 8, bland necrosis. Of the 24, 23 patients died of disease and 1 was alive with disease. The remaining 7 cases were classified as FP, and all were alive without disease. The concordance among 3 pathologists using the criteria was excellent. Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant. The concordance in interpreting the p53 stains by the same 3 pathologists was moderate. The distinction between DMM and FP in a predominantly fibrotic pleural lesion can be made in most cases with adequate sampling and the use of specific criteria.