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In this retrospective study, we evaluated the predictive role of different immunohistochemical expression (IHC) of the mismatch repair proteins (MMR) in patients with colorectal liver metastasis (CRLM) submitted to liver resection. A total of 108 patients were retrieved, and 15 patients were excluded from the study because of the impossibility to obtain adequate formalin-fixed tissue blocks. The final analysis included 93 patients. Twenty-eight cases (30%) presented a no loss of expression or microsatellite stability (MSS) status, 59 cases (63%) showed a hybrid loss of expression, while 6 cases (7%) presented a complete loss of expression or microsatellite instability status (MSI). Patients with complete or hybrid loss of expression of MMR developed a high intra-hepatic recurrence rate compared to other ones (54% vs 21% OR of 4.278, 95% CI 1.53-11.93) (p = 0.004). The same difference in terms of liver recurrence has been found among patients with R0 resection (50% vs 17% OR of 0.2, 95% CI 0.06-0.65) (p = 0.005). However, there was no difference in terms of disease-free survival and overall survival. Complete or hybrid loss of expression of MMR could be considered a risk factor for intra-hepatic recurrences after liver resections for CRLM. [ABSTRACT FROM AUTHOR]