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Background: Melatonin (MLT) is a molecule secreted by the pineal gland in cyclical periods. In mammals, MLT is involved in physiological processes, such as sleep/wake regulation in the circadian cycle. It has antioxidant and anti-inflammatory properties, functions as an immunomodulator, and stimulates bone metabolism. MLT is also involved in tumour processes in breast, prostate, liver, and bone cancers, among others, and in oral cavity tumours like epidermoid carcinoma. We are gradually increasing our knowledge of the underlying mechanism of MLT action in the aforementioned tumour processes, in which MT1, MT2, MT3, and RZR receptors appear to play a highly important role. These receptors belong to a large family of G-protein-coupled transmembrane receptors, some of which have been linked to melatonin's anticancer action, to tumour growth, and to prognosis. The objective of this article is to provide a clear review of research into the range of MLT functions, focusing specifically on MT receptors. We aim to contribute interesting, new approaches to research into oral cavity tumours., Methods: An extensive review of the research literature was conducted using PubMed, Science Direct, ISI Web of Knowledge, and the Cochrane base., Results: This study highlights the growing importance of MLT in the prognosis and treatment of certain tumours, including epidermoid carcinoma in the oral cavity. Moreover, it opens up a highly original, encouraging line of research in the field of tumours., Conclusions: MLT contributes to protecting the oral cavity from tissue damage caused by receptor action. Experimental evidence suggests that it may be useful in the treatment and prognosis of tumour processes in the oral cavity., (© 2011 John Wiley & Sons A/S.)