In an attempt to reduce Carbon Dioxide production, lighting technologies are aiming toward the developing of energetically efficient illumination sources as light-emitting diodes (LEDs). LED lamps emit light at short-wavelengths close to the sensitivity peak of melatonin suppression and expected to further exacerbate circadian disruption and cancer risk from increasing exposure to artificial light-at-night (ALAN). We report the effect of ALAN (1×30 min per night) emitted from yellow incandescent or blue-white LED bulbs and melatonin treatment on urinary 6-sulfatoxymelatonin (6-SMT), tumor growth (volume and mass), and global DNA methylation in 4T1 inoculated Balb/c female mice. Blue ALAN significantly decreased 6-SMT, increased tumor growths, and promoted metastasis formation verses yellow exposure. In blue-treated mice, DNA methylation levels were decreased in tumor and liver cells but not in lung and spleen cells compared with yellow-treated mice. Melatonin treatment inhibited tumor growth, reduced metastasis formation, and equally induced hypermethylation under the two spectral compositions. 6-SMTshowed strong inverse and direct correlations with tumor volume and methylation level, respectively. Finally, melatonin treatment increased relative spleen mass with no spectral differences compared with controls. We demonstrate for the first time that LED lighting can result in aggressive and rapid tumor growth compared with the counterpart incandescent technology, and our results strongly suggest that the mechanism of action by which this occurs is altering DNA methylation levels by ALAN-induced melatonin suppression. These findings further support evidence for the possible association between ALAN and hormone dependent cancer incidences and subsequently advance the need for developing sustainable lighting solutions which are more efficient but less harmful.