The results of this study suggest that melatonin administered topically via cryopass-laser could decrease tumor growth in tumor-bearing mice in a complex manner, specifically affecting SIRT1 expression, which, in turn, modulates and orchestrates different pathways (i.e., PGC-1α/PPARγ pathway and NF-kB signaling) involved in tumor growth and progression. This evidence concerns the gene PPARG and neoplasm.