Melatonin is a relatively recently isolated hormone, produced by the pineal gland. Its implication in several cell functions has augmented interest from scientists worldwide. There is ongoing research investigating the deterrent relationship between melatonin and malignancies and in particular breast cancer. The aim of this article is to review some of the most important findings concerning the effect of melatonin on cancer biology, from both preclinical and clinical studies providing an insight to the complex biological actions of this molecule, as well as their potential significance. The last part concentrates on the oncostatic activities of melatonin on breast cancer and special attention is given on the interplay between melatonin and estrogen. Epidemiological, experimental and clinical evidence indicates that this area is worth further investigation.