The expression of cyclooxygenase 2 (COX-2) protein is increased in many tumours and may be associated with a more aggressive phenotype. We aimed to assess COX-2 expression in a large series of archival mesothelioma specimens. Archival tissue was obtained from 86 malignant pleural mesothelioma samples (histological subtype: 42 epithelial, 28 biphasic and 16 sarcomatoid). Overexpression of COX-2 was detected by immunohistochemical analysis. Positive staining was located in the cytoplasm of malignant tumour cells. Overall 51/86 (59%) tumour sections demonstrated COX-2 overexpression. The frequency varied with histological subtype with 31/42 (73%) of epithelial sections, 14/28 (50%) of biphasic sections and 6/16 (37%) of sarcomatoid sections recorded as positive. Kaplan Meier survival analysis indicated that overexpression of COX-2 was significantly related to improved prognosis (P < 0.001) and was an independent prognostic factor in multivariant analysis. Overexpression of COX-2 protein may confer a survival advantage in mesothelioma patients.