Malignant pleural mesothelioma (MPM) is known to mimic the morphology of a number of diverse neoplastic conditions. WT-1 protein is conventionally used as a positive mesothelioma marker. Recently, a new monoclonal antibody clone WT49 has recently become commercially available. To compare specificity and sensitivity of the conventionally used clone 6F-H2 for the diagnosis of MPM to those of the new clone WT49. Forty cases of MPM, and 55 cases of lung carcinoma, 10 cases of synovial sarcoma of the intrathoracic region were analyzed. Of the 40 cases of MPM tested, clone WT49 and 6F-H2 stained 30 (75.0%) and 26 (65.0%) cases, respectively. Nuclear staining of clone WT49 was observed in 4 (7.2%) cases of lung carcinomas and in 1 (10.0%) case of synovial sarcoma. However, there was no nuclear staining of clone 6F-H2 in lesions other than MPM. There was no cytoplasmic staining of clone WT49 in any tumor. However, cytoplasmic staining of clone 6F-H2 was observed in 7 (17.5%) cases of MPM, 17 (30.1%) cases of lung carcinomas, and 5 (50.0%) cases of synovial sarcoma. The main advantage of WT49 is its higher reactivity with the sarcomatoid area of biphasic mesothelioma, but the results also indicate 1 drawback, that this clone was seen to react with a small percentage of lung carcinomas when it is used to distinguish epithelioid mesotheliomas from lung carcinomas. Furthermore, the positive reaction of clone WT49 was restricted to nucleus without cytoplasmic staining, which is seen in conventionally used WT-1 antibodies.