AIM: The relationships between microsatellite instability (MSI) and survival in colorectal cancer patients are not consistent. The favorable survival of patient with MSI has been suggested to be related to pronounced inflammatory infiltration; however, the reason for non-association of MSI with survival is unclear. Our aims were to investigate the associations of inflammatory infiltration and tumor necrosis (TN) with microsatellite status and clinicopathological factors in colorectal cancer patients in whom MSI was not related to survival.METHODS: Three hundred and one colorectal adenocar cinomas were evaluated for inflammatory infiltration and 300 for TN under light microscope. RESULTS: Low infiltration at invasive margin (x2 = 3.94,P= 0.047) and in whole tumor stroma (x2 = 3.89, P= 0.049) was associated with MSI, but TN was not (x2=0.10,P = 0.75). Low infiltration was related to advanced stage (x2 = 8.67, P = 0.03), poorer differentiation (x2 = 8.84, P = 0.03), DNA non-diploid (x2= 10.04, P = 0.002), higher S-phase fraction (x2 = 11.30, P = 0.004), positive p53 expression (x2 = 7.94, P = 0.01), and worse survival (P = 0.03 for both univariate and multivariate analyses). Abundant TN was related to advanced stage (x2 = 17.74, P = 0.001) and worse survival (P = 0.02 for univariate, and P = 0.05 for multivariate analysis). CONCLUSION: The result that high inflammatory infiltration was not related to MSI might help explain the non-association of MSI with survival in colorectal cancer patients.