Simian virus 40 (SV40) has been detected in different human tumours in numerous laboratories. The detection of SV40 in human tumours has been linked to the administration of SV40-contaminated polio vaccines from 1954 until 1963. Many of these reports linked SV40 to human mesothelioma. Some studies have failed to detect SV40 in human tumours and this has caused a controversy. Here we review the current literature. Moreover, we present evidence showing how differences in the sensitivities of methodologies can lead to a very different interpretation of the same study. The same 20 mesothelioma specimens all tested negative, 2/20 tested positive or 7/20 tested positive for SV40 Tag by simply changing the detection method on the same immuno-precipitation/western blot membranes. These results provide a simple explanation for some of the apparent discordant results reported in the literature.