Platelets play a central role in inflammation through their direct interaction with other cell types, such as leukocytes and endothelial cells, and by the release of many factors, i.e. lipids [such as thromboxane(TX)A2 ], proteins(a wide number of angiogenic and growth factors) stored in α-granules, and adenosine diphosphate(ADP), stored in dense granules. These platelet actions trigger autocrine and paracrine activation processes that lead to leukocyte recruitment into different tissues and phenotypic changes of stromal cells which contribute to the development of different disease states, such as atherosclerosis and atherothrombosis, intestinal inflammation and cancer. The signals induced by platelets may cause pro-inflammatory and malignant phenotypes in other cells through the persistent induction of aberrant expression of cyclooxygenase(COX)-2 and increased generation of prostanoids, mainly prostaglandin(PG)E2 . In addition to cardiovascular disease, enhanced platelet activation has been detected in inflammatory disease and intestinal tumourigenesis. Moreover, the results of clinical studies have shown that the antiplatelet drug aspirin reduces the incidence of vascular events and colorectal cancer. All these pieces of evidence support the notion that colorectal cancer and atherothrombosis may share a common mechanism of disease, i.e. platelet activation in response to epithelial (in tumourigenesis) and endothelial (in tumourigenesis and atherothrombosis) injury. Extensive translational medicine research is necessary to obtain a definitive mechanistic demonstration of the platelet-mediated hypothesis of colon tumourigenesis. The results of these studies will be fundamental to support the clinical decision to recommend the use of low-dose aspirin, and possibly other antiplatelet agents, in primary prevention, i.e. even for individuals at low ardiovascular risk. This article is protected by copyright. All rights reserved.