Background: Colorectal cancer (CRC) is a common malignancy worldwide and a leading cause of cancer-related deaths. The molecular basis of CRC can guide patient prognosis and therapy. Unfortunately, knowledge on the CRC mutation landscape is limited. In this study, we investigated the mutation profile of related genes by next-generation sequencing and associated with microsatellite instability (MSI) in a series of 43 Brazilian CRC patients from 2016 to 2022, of a Public Oncology Hospital. This study aimed to analyze the frequency of mutation covariates of the KRAS and BRAF genes and their correlation with survival data in patients diagnosed with metastatic RCC. Methods: We conducted a retrospective, observational and descriptive study in 43 patients diagnosed with CRC treated at an Oncology Reference Hospital in Brazil. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tumor tissues. Targeted sequencing was performed using a customized panel for CRC-related genes. The mutation data was analyzed in relation to clinicopathological features, MSI status and survival, using the Kaplan-Meier method and log-rank test. Results: RAS mutations were found in 37.2% of patients and BRAF mutations in 9.3%. The analysis of most secondary clinicopathological features did not show statistical prognostic impact. In general analysis, the age and presence of BRAF mutation were related to the increased risk of death HR-0.31 (0.11-0.82). However, among patients with BRAF mutations exclusively, the age did not represent an increased risk of death. Concerning our RAS mutations, as we already knew from previous literature data, the variety is diverse. We noticed nine different RAS alterations, in which the most prevalent was the G12D (33%), followed by G13D, Q61K and G12A. The distribution of our RAS alteration and prevalence is summarized in the table below: Conclusions: Our findings are consistent with previous studies concerning frequency and patterns of RAS and BRAF mutations in CRC. The identification of MSI and the evaluation of genetic ancestry may help to guide treatment decisions in CRC patients. At present, it is already known that some of RAS mutations are targets for selective RAS drugs and may have better outcomes the pan-RAS drugs. Our study provides important insights into the mutation profile of related genes in Brazilian CRC patients and these findings have implications in clinical management of CRC. Further studies with larger cohorts are needed to validate our findings.