: Melatonin has shown the potential to inhibit growth of different tumors, both in vitro and in vivo. There is clear evidence that the administration of melatonin alone or in combination with chemo and radiotherapy in cancer patients with advanced solid tumors has been associated with improved outcomes of tumor regression and survival. Moreover, chemotherapy has been shown to be better tolerated in patients treated with melatonin. However, there are different ways of preparation and administration of melatonin to the patient. This review article aims to offer the insight into the preparation, biological features and clinical findings in its use in cancer patients. Melatonin (MLT) can only be solubilized in water at 40-45 °C; at other temperatures it can only be solubilized in alcohol. It is absorbed in the human body complexed with adenosine by a hydrogen bond. It acts on two common denominators: proliferation and differentiation; in addition to anticancer homeostasis, MLT has a documented antidegenerative and immunomodulatory role. It also plays an important role in limiting oxidative stress, affecting blood and bone marrow constituent ratio, leukocyte formula regulation, hemoglobin synthesis, platelet genesis, aggregation and in erythrocyte resistance. Despite of all these important roles, most well-known features are probably the least important ones, such as sleep and wakefulness regulation and its effect on jet lag. In the preparation formulated by Prof. Di Bella, melatonin with adenosine at a ratio of 1:4, stabilized with 30% of glycine (MLT-DBM), has been used since 1994 in many patients with various indications and positive therapeutic responses and a total absence of toxicity. This method can be a good alternative to commercially produced preparations, as it was scientifically proved and published worldwide at conferences and in various medical journals.