Pleural Malignant Mesothelioma (MM) is a highly aggressive neoplasm with a poor survival rate, hard diagnosis and treatment. The incidence of MM in Western Europe countries is expected to increase drammatically in the next 10-15 years. In spite of this drammatic scenario, at this time the only instruments for screening and early diagnosis are based on radiological tests with evident ethical and economical problems. For this reason, some authors are evaluating biological indicators with the significance of screening and early diagnosis markers. One of the most promising marker is serum mesothelin (SMRP). SMRP levels appeares to be significantly related to MM and its clinical (diagnostic/prognostic) usefulnes has been suggested. The purpose of this research is to show SMRP trend in relation both to the course of the disease and the response to therapies in some Epithelioid MM patients. The analysis of SMRP levels in these patients suggests that it may be a useful marker for monitoring the response to treatment. In fact, it was observed that SMRP increases in patients who did not respond to therapy, it tends to remain stable when therapies results into a clinical stabilization, while it decreases after surgical procedure and in case of clinical improvement.