Heterogeneous nuclear ribonucleoprotein B1, an RNA-binding protein required for mRNA maturation, reportedly is overexpressed in early lung cancer and in several other tumors, including precancerous lesions. Expression of the protein was assessed immunohistochemically in 39 specimens of malignant mesothelioma and five of non-neoplastic pleura, and by flow cytometry in a human epithelioid mesothelioma cell line. No tumor showed overexpression, but 29 of 39 cases showed modest expression. Patients whose tumors showed expression had significantly better survival rates than others. Epithelioid tumors and reactive mesothelial cells were more likely to express the protein than sarcomatoid tumors and resting mesothelial cells. Flow cytometric analysis of an epithelioid mesothelioma cell line demonstrated stronger expression in exponentially growing than growth-restricted cells. Heterogeneous nuclear ribonucleoprotein B1 is expressed widely in malignant mesotheliomas and in reactive mesothelial cells, but is not overexpressed. This protein may regulate proliferation linked with differentiation toward epithelioid morphology in mesothelial cells. Expression of the protein may be a prognostic indicator for patents with malignant mesothelioma.