Colorectal cancer is one of the most common malignancies, often presenting with a poor prognosis. To date, the anatomic extent of disease has been by far the most important prognostic factor. Recently, we obtained evidence that the type, density, and location of immune cells in colorectal cancer could provide a prognostic factor superior and independent to that of criteria related to the anatomic extent of the tumor. Here, we discuss the meaning and potential implications of this novel finding.