Ivo P. Janecka Health Research International Boston, MA. Abstract Background: Colon cancer is among the leading causes of cancer mortality and its incidence is increasing worldwide. This is true in spite of broad basic research into colon cancer while, concurrently, physical activity has been shown to offer significant preventive potential. This background led to the formulation of the following research questions: Why is physical activity so effective in decreasing the incidence of colon cancer?Is there a common denominator to colon cancer and physical activity, which has a reciprocal function?Knowing the potential for public health impact of physical activity on colon cancer, has physical activity-colon cancer relationship been in the forefront of research efforts? Methods: Content analysis of archival literature has been carried out on census of 32,822 message units, extracted from the National Library of Medicine and its PubMed database. The following search terms were used: colon cancer, physical activity, melatonin, age/genetics, diet (obesity, vitamin D, calcium), immunity/inflammation, and bioactive substances incorporating insulin-like growth factor 1, interleukins, and prostaglandins. The research timeframe for each category began with the first article published and ended with the last one printed in 2005. Results/Conclusions: The effectiveness of physical activity in decreasing the incidence of colon cancer is likely the result of its biologic activity within not one or two but all of the major known colon cancer etiologies, demonstrating a powerful reciprocal relationship. Melatonin is identified as a plausible common denominator of colon cancer and physical activity. The greatest volume of publications deals with colon cancer and genetics. A significant societal health care impact could be achieved by adopting physical activity as a major cancer control strategy.