Objective: RAS genes are members of the RAS/Mitogen activated protein kinase pathway which is induced by Epidermal Growth Factor Receptor (EGFR). Mutations in genes in this pathway trigger cancer development. In colorectal cancer, mutations in RAS genes cause resistance to EGRF- targeted therapy. In the treatment of metastatic colorectal cancer, EGFR’s monoclonal antibodies are widely used as chemotherapeutic agents. Kirsten-RAS mutations are found in 30-50% and N-RAS mutations are found in 2-3% of colorectal cancer. In this study, we aimed to analyze Kirsten-RAS /N-RAS mutations in patients with metastatic colorectal cancer. Methods: One hundred of metastatic colorectal cancer patients resistant to EGFR- targeted therapy were scanned for the Kirsten-RAS mutations status (exon 2,3,4) and N-RAS mutation status (Exon 2,3,4) by Real-Time PCR (Polymerase Chain Reaction) method. Results: As a result of this study, Kirsten-RAS mutation was found 48% and N-RAS mutation was 1.92%. The most common Kirsten-RAS mutations were in codon 12. The distribution of codon 12 mutations were obtained as G12V (25%), G12D (23%), G12C (14.5%). Conclusion: In our study, the frequencies of Kirsten-RAS and N-RAS mutations were compitable with similar reports. Our results have supported that testing RAS genes mutations have a vital role in identifying patients who benefit from Epidermal Growth Factor Receptor- targeted therapy.