Background: Apart of medical reasons, a definitive diagnosis of malignant mesothelioma may be required as a basis for a claim of financial compensation although a pathological source of conclusive evidence is missing. Clinical assessment of all available data is then the only option to come to a final conclusion. We evaluated the diagnostic work-up of a large cohort of Dutch patients who applied for financial compensation due to mesothelioma. We determined how often a pathological or clinical diagnosis can be made, and which factors are associated with making the final diagnosis malignant mesothelioma. Methods: A flow diagram of the diagnostic work-up was constructed for patients that applied to the Dutch institute for asbestos victims between 2005 and 2008 (N=1498). Both pathological and clinical factors that may influence the diagnostic outcome were assessed. Results: In 97 of the 1498 patients (6%) no pathologic diagnosis could be established because of an uncertain diagnosis (N=54), inadequate (N=22) or unavailable tumor samples (N=21). A final pathological diagnosis of malignant mesothelioma could most often be made when biopsy samples were available compared to those in whom only cytological material was available. In patients in who no conclusive diagnosis could be made, clinical assessment was performed. Eighty percent of patients (66/83) who were clinically assessed were considered to have mesothelioma. None of the clinical features analyzed were strongly associated with a confirmed diagnosis of malignant mesothelioma. Discussion: Our study shows that only in a small number of the patients who applied no pathologic diagnosis could be obtained. Based on judgment of clinical experts in the majority of these cases a near to certain diagnosis could be made. Moreover, it is reasonable to obtain biopsy material from patients to increase the chance to obtain a confirmed diagnosis. Therefore, it is important to refer patients early for diagnostic procedures. (C) 2013 Elsevier Ireland Ltd. All rights reserved.