Background: Genetic evaluation is essential in assessing colorectal cancer (CRC) and colorectal liver metastasis (CRLM). The aim of this study was to determine the pragmatic value of KRAS on oncological outcomes after CRLM according to the ESMO recommendations and to query whether it is necessary to request KRAS testing in each situation. Methods: A retrospective cohort of 126 patients who underwent surgery for hepatic resection for CRLM between 2009 and 2020 were reviewed. The patients were divided into three categories: wild-type KRAS, mutated KRAS and impractical KRAS according to their oncological variables. The impractical (not tested) KRAS group included patients with metachronous tumours and negative lymph nodes harvested. Disease-free survival (DFS), overall survival (OS) and hepatic recurrence-free survival (HRFS) were calculated by the Kaplan–Meier method, and a multivariable analysis was conducted using the Cox proportional hazards regression model. Results: Of the 108 patients identified, 35 cases had KRAS wild-type, 50 cases had a KRAS mutation and the remaining 23 were classified as impractical KRAS. Significantly longer medians for OS, HRFS and DFS were found in the impractical KRAS group. In the multivariable analyses, the KRAS mutational gene was the only variable that was maintained through OS, HRFS and DFS. For HRFS (HR: 13.63; 95% confidence interval (CI): 1.35–100.62; p = 0.010 for KRAS), for DFS (HR: 10.06; 95% CI: 2.40–42.17; p = 0.002 for KRAS) and for OS (HR: 4.55%; 95% CI: 1.37–15.10; p = 0.013). Conclusion: Our study considers the possibility of unnecessary KRAS testing in patients with metachronous tumours and negative lymph nodes harvested. Combining the genetic mutational profile (i.e., KRAS in specific cases) with tumour characteristics helps patient selection and achieves the best prognosis after CRLM resection
