Background The differential diagnosis between malignant mesothelioma (MM) and metastatic lung adenocarcinoma (MLA) often relies on immunohistochemical studies, with no individual immunomarker holding satisfactory discrimination ability.

Methods We investigated the diagnostic accuracy of CD24 immunoreactivity on 134 patients including 69 cases of MM and 65 MLA.

Results The expression of CD24 favoured MLA, with 57/65 cases showing positive cytoplasmic staining compared with 9/69 MM (p<0.001), whose immunopositivity pattern was prevalently membranous (7/9 cases).

Conclusions CD24 positivity can accurately discriminate MM from MLA. Prospective studies are warranted to clarify whether CD24 could integrate with other immunomarkers to facilitate the diagnosis of mesothelial malignancies.