Recent observations showed that host may regulate either endocrinologically or immunologically tumor growth and differentiation, perhaps by modulating oncogene expression. Within the endocrine system, the pineal hormone, melatonin, seems to play an important antineoplastic role. To investigate its secretion in relation to tumor growth, we have evaluated the daily serum levels of melatonin in a group of 25 untreated breast cancer patients with a locally limited disease. Tumor cell proliferation was established by measuring Ki-67 labeling rate. As controls, 46 healthy women were considered. Breast cancer patients showed significantly higher mean values of melatonin than controls. Moreover, patients with negative Ki-67 labeling rate had significantly higher levels of the pineal hormone than those with a positive Ki-67 rate. Since tumors with high growth fraction present a worse prognosis, this study would suggest that the relief of an increased melatonin secretion represents a favorable prognostic sign, because of its association with less proliferating breast cancers.