OBJECTIVE The association between asbestos exposure and the development of malignant mesothelioma is well known. Nonetheless, a proportion of patients suffering from this disease do not appear to have documented exposure to asbestos fibers from any known source. Available information suggests that a true "background" incidence of this disease exits raising the possibility that other factors contribute to its etiology. This paper will review existing data related to non-asbestos related mesothelioma and suggest avenues for further research. METHODS A comprehensive electronic MEDLARS search of the literature pertinent to non-asbestos related malignant mesothelioma was performed including the years 1996-2001. Hand searches were also carried out to supplement electronically derived information and literature pre-dating 1996. The resulting references were stratified into the following categories and reviewed; (1) radiation associated mesothelioma, (2) familial mesothelioma, (3) dietary factors, (4) childhood mesothelioma and (5) the role or SV40. RESULTS Available information suggests that genetic factors may play a larger role in the etiology of this disease than currently appreciated. The interplay of genes and environment require further elucidation in the pathogenesis of mesothelioma. The role of diet is poorly understood with few studies directly addressing this issue. Whether other environmental or infectious agents are involved in mesothelioma development remains speculative. CONCLUSIONS The biology of mesothelioma is an enigma. Although this disease appears to occur in the absence of asbestos exposure, the genetic and biological differences between asbestos related and non-asbestos related tumors is unclear. Additional epidemiological and laboratory studies are needed to provide a better understanding of the relationship between environmental and non-environmental causes of mesothelioma.