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Introduction KRAS mutation status in codons 12 and 13 is recognized as a predictive factor for resistance to anti- EGFR monoclonal antibodies. Recent retrospective studies suggested that patients (pts) with different KRAS mutations (KRAS mts) respond different to specific systemic therapy and also pts with KRAS mt in codon 13 might respond to anti- EGFR monoclonal antibodies but with lower response rates than pts with KRAS wild-type (KRAS wt) tumors. Methods Objective response (OR), time to progression (TTP), overall survival (OS) and BRAF status in metastatic colorectal cancer (mCRC) pts treated with first- line therapy according to KRAS status, were retrospectively analyzed. Results In total 176 mCRC pts who received first- line therapy between May 2009 and October 2010 were included in retrospective analysis. The median age was 62 years (27- 86), M/F 61/39 %. The most common received therapies were XELIRI/bevacizumab and XELOX/cetuximab in 29.5 % and in 22.1 % of pts respectively. KRAS mts were found in 63 pts (35.8 %), mt KRAS in codon 12 in 53 pts (84%) and mt KRAS in codon 13 in 10 pts (16%). BRAF V600E mt was detected in 13 of 176 pts (7.4%). OR in wt KRAS/wt BRAF pts was 54% (CR 14.7 %, PR 39.3 %) and in wt KRAS/mt BRAF pts was 38.5% (CR 15.4 %, PR 23.1 %), difference (diff) was not statistically significant (p= 0.378). Median OS of wt KRAS/wt BRAF pts and wt KRAS/mt BRAF pts was 107.4 months (mo) (95% CI: 82- 132.9 mo) and 45 mo (95% CI: 28.4- 61.5 mo) respectively, diff was statistically significant (p= 0.042). TTP in wt KRAS/ wt BRAF pts and wt KRAS/mt BRAF pts was 16 mo (95% CI: 10.7- 21.2 mo) and 12 mo (95% CI: 4.0 -15.0 mo) respectively, diff was not statistically significant (p= 0.558). OR in codon 12 mt pts was 47% (CR 20.7%, PR 26.3%) and in codon 13 mt pts was 33% (CR 11%, PR 22%),dif was not statistically significant (p= 0.08). TTP in mt codon 12 pts and mt codon 13 pts was 13.5 mo (95% CI: 9.0- 18.0 months) and 9.3 mo (95% CI: 5.1- 13.5 mo) respectively, diff was not statistically significant (p= 0.106). Conclusion Mt BRAF pts have statistically significantly worse prognosis than wt BRAF pts, with lower response rates and progress earlier during systemic treatment. Codon 13 mt KRAS pts have lower response rate and progress earlier than KRAS codon 12 mt pts. Definitive role of mt BRAF and different KRAS mts are needed to be defined to select pts, who will benefit from specific combination of systemic therapy.