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Reserpine was being widely used as a well-established, beneficial treatment for hypertension, when three studies, published in 1974 in the same issue of the Lancet, suggested that reserpine users, compared with non users, had a threefold to fourfold increased risk of developing breast cancer. These results were subsequently contradicted by the results of nine other studies, published between 1975 and 1980. In a recent review of all those studies, the initial causal association was deemed erroneous, although the reasons for the falsely positive results were not identified. Recently, however, one study done by Horwitz and his colleagues in Yale University claimed that the false association might have been produced by a phenomenon called exclusion bias that were probably happened because patients with cardiovascular disease were rejected as possible controls in the original reserpine-breast cancer case-control study. This paper summarizes the results of those studies resulted in positive and negative associations between the use of reserpine and breast cancer, and reviews the methodological variations of the studies.