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Several factors including population aging, poor dietary habits, obesity, insufficient physical activity, and smoking can explain its increased prevalence. CRC is a heterogeneous disease both histopathologically and in term of its molecular and genetic aspects. Melatonin a derivative of tryptophan, is synthesized and released from pineal gland but it is also found in numerous extrapineal tissues including retina, testes, lymphocytes, Harderian gland, gastrointestinal tract, etc. This molecule has several tasks which enhance physiological functions such as antioxidant, antiaging, immunomodulatory, and tumor inhibition. Multiple immunocytochemical studies reported melatonin in the intestinal mucosa where its concentration is greater than in the blood. These findings suggest that melatonin may have a potential inhibitory role in CRC progression. 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