Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. The epidermal growth factor receptor (EGFR) is relevant in the development and progression of CRC, because it is part of multiple signaling pathways involved in processes of the cell cycle, their malfunction causes dysregulation and subsequently carcinogenesis. Consequently, therapies were developed with anti-EGFR monoclonal antibodies (MAbs) that improve the survival of patients with CRC. However, mutations in the oncogenes Kirsten rat sarcoma (KRAS) and Neuroblastoma RAS (NRAS), modulators of the EGFR signaling pathway (downstream) activate a pathway independent in which such drugs have no effect. Patients with these mutations have a low response to MAb therapies. In this research, the SNaPshot sequencing method was used for the first time in Venezuela for the diagnosis of mutations in exon 2 of the KRAS and NRAS genes, from DNA extracted from tumor tissue samples fixed with formalin and included in paraffin (FFPE) and was compared with Sanger’s method to determine the specificity and sensitivity, in the detection of mutations in the KRAS and NRAS genes. Of the 33 samples analysed, 27.3% presented mutations in KRAS and 15.1% in NRAS. With the obtained, it was carried out for the first time in the country the assignment of the geographical distribution of the polymorphisms found in these genes. The mutational status of the KRAS and NRAS genes showed no relationship statistically significant with clinical-histopathological variables. For this study, the SNaPshot method showed greater accuracy, sensitivity and specificity in the detection of single nucleotide polymorphisms than the Sanger method.