PURPOSE: This review proposes an overall vision of the protective and therapeutic role of melatonin in breast cancer: from the specific cases of blind women and their reduction of breast cancer incidence to all clinical uses of the sleep hormone in breast cancer. METHODS: We reviewed studies focused on (1) the correlation between blindness and breast cancer, (2) the correlation between melatonin and breast cancer occurrence in the general population, (3) melatonin therapeutic use in breast cancer, and (4) we discussed the properties of melatonin that could explain an anticancer effect. RESULTS: (1) Seven studies of breast cancer risk in blind women related significant incidence decreases, up to 57%, among totally blind women. The limited number of studies and the absence of adjustment for confounding factors in most studies limit conclusions. None of these studies established melatonin profiles to determine whether blind women with a decreased breast cancer incidence produced higher levels of melatonin. (2) In the general population, 5 meta-analyses and 12 prospective-cohort studies focused on melatonin levels at recruitment and breast cancer occurrence. All reported the absence of correlation in premenopausal women, whereas in postmenopausal women, most studies showed significantly decreased risk for women with highest melatonin levels. (3) The therapeutic interest of melatonin associated with chemotherapy, radiotherapy, and hormonotherapy is poorly documented in breast cancer to conclude on a positive effect. (4) Melatonin effects on mammary carcinogenesis were only reported in in vitro and animal studies that demonstrated antiestrogenic, antioxidant, oncostatic, and immunomodulatory properties. CONCLUSION: The preventive role of high endogenous melatonin on breast cancer as well as its beneficial therapeutic use remains to be proven.