Melatonin inhibits tumor genesis in a variety of in vivo and in vitro experimental models of neoplasia. In industrialized societies, light at night, by suppressing melatonin production, poses a new risk for the development of a variety of cancers such as breast cancer. This effect on skin has been previously studied only in animals and not in humans. Our goal was to examine the relationship between 24-hour 6-sulphatoxymelatonin levels and skin cancer in a case-control study of 70 patients with skin cancer and 70 healthy individuals. The level of 6-sulfatoxymelatonin was measured in 24-hour urine by the ELISA method. In the case group, 55 (78%) patients had basal cell carcinoma and 15 (22%) had squamous cell carcinoma. The mean level of 24-hour urine 6-sulfatoxymelatonin was significantly higher in the control group (P<0.001). Also, sleep duration had a significant difference between the two groups (P=0.001). It seems that a low level of 24-hour urinary 6-sulfatoxymelatonin renders human beings prone to skin cancer. This association, however, requires further investigation.