Caffeine (1,3,7-trimethylxanthine, also abbreviated to CAF) is a natural chemical with stimulant effects and is commonly included in many drinks and foods, including coffee, tea, cola, energy drinks, cocoa, chocolates, and so on. Our group previously reported that oral administration of CAF efficiently suppressed the development of intestinal inflammation in a dextran sulfate sodium (DSS)-induced murine acute colitis model by suppressing the expression of chitinase 3-like 1, one of the mammalian chitinases without enzymatic activity. Chitinases are hydrolytic enzymes that break down chitin, a polymer of N-acetylglucosamine, and chitinase-like proteins have no enzymatic activity with preserving chitin-binding ability. CAF binds a cleft of the chitinase active site and plays a role as a pan-chitinase inhibitor. Although CAF showed an anti-inflammatory effect in the above model, oral administration of low-dose CAF with 10% sucrose showed potentially neoplastic effects in colonic epithelial cells in a DSS-induced murine chronic colitis model. In this review, we would like to discuss the pros and cons of coffee/CAF in colonic inflammation and neoplasia with an example of pathological finding.