The authors describe the case of a 70 year-old asymptomatic female, who showed nodular pleural growths at an occasional chest roentgenogram. Histological examinations and laboratory findings excluded the possibility of an inflammatory granulomatous process, but they did not allow differentiation between malignant sarcomatoid pleural mesothelioma and malignant fibrous histiocytoma. Only at immunohistochemistry was the differential diagnosis made. In fact, the co-expression of vimentin and cytokeratins by neoplastic cells, along with their negativity for macrophage markers strongly supported the hypothesis that the neoplastic growth originated from subpleural mesenchymal stem cells.