Immunohistochemistry (IHC) is used to help differentiate pleural mesothelioma from pulmonary adenocarcinoma in pleural biopsies and cytology specimens of pleural effusions due to overlapping morphologic features between these two malignancies. The aim of this study is to evaluate IHC glypican-1, a recently proposed marker for epithelioid mesothelioma, in our cohort of mesotheliomas and pulmonary adenocarcinoma. Tissue microarrays with duplicate cores from 33 cases of mesotheliomas (28 epithelioid type and five sarcomatoid type) and 21 cases of pulmonary adenocarcinoma were stained with glypican-1 antibody. The proportion of cases by tumor type showing staining with glypican-1 and the H-score for each tumor type were evaluated. All 33 cases of mesothelioma and all 20 cases of pulmonary adenocarcinoma with interpretable cores showed positive cytoplasmic staining. All but one case of mesothelioma and all pulmonary adenocarcinomas showed staining in at least 80% of the tumor cells. The mean H-score for glypican-1 of mesothelioma (134 +/- 59, mean +/- SD) was not significantly different from that for pulmonary adenocarcinoma (156 +/- 60; P = 0.21). Neither epithelioid type (mean H-score 135 +/- 57) nor sarcomatoid type (mean H-score 130 +/- 78) of mesothelioma showed different H-scores when compared to pulmonary adenocarcinoma (P = 0.23 and 0.42, respectively). In conclusion, glypican-1 IHC does not differentiate mesothelioma from pulmonary adenocarcinoma.