Most observational studies show an association between melatonin and cancer in humans. We conducted a systematic review of randomized controlled trials (RCTs) of melatonin in solid tumor cancer patients and its effect on survival at 1 yr. With the aid of an information specialist, we searched 10 electronic databases from inception to October 2004. We included trials using melatonin as either sole treatment or as adjunct treatment. Prespecified criteria guided our assessment of trial quality. We conducted a meta-analysis using a random effects model. We included 10 RCTs published between 1992 and 2003 and included 643 patients. All trials included solid tumor cancers. All trials were conducted at the same hospital network, and were unblinded. Melatonin reduced the risk of death at 1 yr (relative risk: 0.66, 95% confidence interval: 0.59-0.73, I2=0%, heterogeneity P<or=0.56). Effects were consistent across melatonin dose, and type of cancer. No severe adverse events were reported. The substantial reduction in risk of death, low adverse events reported and low costs related to this intervention suggest great potential for melatonin in treating cancer. Confirming the efficacy and safety of melatonin in cancer treatment will require completion of blinded, independently conducted RCTs.