In a blinded cross-over design, we studied whether three pathologists were biased by clinical information when making histopathological diagnoses of adenocarcinoma of the lung and benign and malignant mesothelial tumours. Furthermore, the interobserver variation of these diagnoses was assessed. Forty-one cases of adenocarcinoma of the lung and mesothelial tumours were assessed by three pathologists in four rounds. In the first two rounds, slides stained by H&E and clinical information were available. Slides and information were matched so that a specific slide in one round was given clinical information suggesting adenocarcinoma and in the other round, the clinical information suggested mesothelial tumour. In the third and fourth rounds, a panel of immunohistochemical stains was added. The clinical information was matched in the same way as in the first and second rounds. Bias by clinical information was observed when the diagnoses were made on slides stained by H&E, while no bias could be demonstrated when immunohistochemical reactions were included. The reproducibility also improved significantly when these slides were available.