Background: Melanoma is the most aggressive skin cancer type and is responsible for 80% of deaths from this entity. It is considered one of the tumors with the highest mutational load, with approximately 50% of cases in codon 600 of the BRAF gene. Objective: To determine the frequency of BRAF V600E/E2/D and BRAF V600K/R/M mutations in patients with malignant melanoma unresectable stage III-IIIC – IV, during the period May-2018 and August-2021, at UNIGEM, in Medellín. Methodology: Observational, retrospective study, which included 154 paraffin-embedded biopsies from patients with stage III-IIIC-IV unresectable malignant melanoma. The evaluation of the BRAF V600E/E2/D and BRAF V600K/R/M mutations was carried out through real-time PCR using the Idylla platform. Results: 154 test results for the BRAF V600 mutation were reviewed, with a total of 60 (38.9%) mutated cases, of which 56 (93.3%) correspond to the V600E/E2/D change, predominantly in minors or equal to 63 years of age. Conclusion: We found that in the population analyzed with metastatic melanoma, 38.9% of the patients presented alterations in the BRAF gene, more frequently in men, in the V600 E/E2/D codon and in the age group≤63 years.