Over the past eight years an increasing number of investigators have found SV40 genomic sequences in a variety of human samples, both malignant and normal. Tumor types recurrently reported as SV40-positive include choroid plexus neoplasms, ependymomas, osteosarcomas, and mesotheliomas. Nonetheless, considerable skepticism that SV40 is a human pathogen still prevails. More constructively, the study of SV40 in humans has renewed interest in the related BK and JC viruses and their role in human disease. New questions now must be addressed. In particular,seroepidemiologic studies utilizing reagents that distinguish SV40, BKV, and JCVimmune responses would be a logical next step for independently assessing viral prevalence. Also, prospective studies of select patient groups using optimized detection methods might determine whether SV40 is associated with human oncogenesis in particular circumstances. The importance of such research is underscored by the potential to prevent human polyomavirus infections, and possible associated malignancy, through immunization of high risk populations.