Immunohistochemistry is frequently employed to differentiate between malignant mesothelioma (MM) and pulmonary adenocarcinoma (AC) infiltrating the pleura, but there is uncertainty as to which antibodies are most useful. The present study investigated the presence of the serine protease, maspin, in epithelioid MMs and evaluated the diagnostic utility of maspin for the differential diagnosis between epithelioid MM and pulmonary AC with pleural involvement. The results showed more frequent maspin immunostaining among AC cases compared with MM cases. Maspin positivity was significantly higher among AC cases with respect to both the extent and intensity of staining. A significant difference also existed between the two tumour types with respect to the overall maspin score. Despite these findings, the sensitivity and specificity of maspin positivity to detect AC were only 59% and 73%, respectively, indicating that detection of maspin is of no value for the differential diagnosis of AC and MM.