Background:The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II–III CRC patients.Methods:We constructed a tissue microarray from 196 consecutive patients with stage II–III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models.Results:Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs −, ⩽2 cells per spot) and CD68 (+, >0 vs −, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57−), or high (CD68−/CD57−) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3–5.8) and 9.0 (3.2–25.4) for RFS, and 2.5 (1.2–5.1) and 10.6 (3.8–29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71–91), 65% (54–74), and 12% (2–47), respectively, for RFS, and 91% (80–96), 76% (66–84), and 25% (7–59), respectively, for OS.Conclusion:Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II–III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.