Our aim was to systematically review the epidemiologic evidence for an association of circulating interleukin-6 (IL-6), an inflammatory cytokine and cancer. We systematically searched electronic databases Embase, Medline and Web of Science for the studies of circulating IL-6 and any form of cancer. We identified and reviewed 189 discrete studies, consisting of 177 prevalent studies and three prospective studies. Cancer patients' IL-6 concentrations were higher than healthy controls' in most studies, but the results of investigations comparing IL-6 in cancer patients and individuals with benign diseases were less consistent. Due to the small number of prospective studies it is impossible to determine whether IL-6 is causally related to cancer. Large prospective studies of circulating IL-6 or studies using the functional variants of the IL-6 gene as instruments for circulating IL-6 concentrations would provide information on possible aetiological links between IL-6 and malignancy.