: Studies on the relationship between the pineal gland, melatonin and neoplastic disease have recently become one of the most fascinating aspects of pineal research. The first data suggesting a link between the pineal and cancer were published 70 years ago. However, the real progress in this area of research has been made in the last two decades. The bulk of the experimental evidence indicates the influence of the pineal gland on the malignant tumor formation and/or growth. The majority of reports point toward the oncostatic action of the pineal, exerted most probably by its hormone, melatonin, via different mechanisms, including modulation of endocrine and immune systems and direct antiproliferative action. The mechanisms of the oncostatic action of the pineal seem to be, however, very complex. There is some indication that the pineal gland may also play a role in human malignancy. Alterations in melatonin concentrations have been demonstrated in various tumor types including breast cancer, prostate cancer, colorectal carcinoma, and uterine cancer. Moreover, melatonin has been reported to be helpful in therapy of advanced cancer of various types. However, detailed 24h melatonin profiles must be studied in large numbers of patients with different types of tumors before determining whether melatonin concentrations have any diagnostic and/or prognostic values in cancer patients. Moreover, well designed clinical trials should be performed on the possible therapeutic significance of melatonin in neoplastic disease.