Introduction: Colorectal cancer (CRC) represents a global issue, taking into consideration its frequency. Treating of patients with metastatic colorectal cancer (mCRC) is a very complex process. It has been proven that, in addition to pathohistological and molecular characteristics, the localization of the primary tumour (LPT) also affects the overall survival. Although considered a single organ, segments of the colon differ from each other, histologically, physiologically, and molecularly. It is known that a certain percentage of patients with RAS / RAF wild type (wt) tumour type, however, does not respond to anti-EGFR therapy. The reasons may be a consequence of primary or secondary resistance, but also excessive expression of HER2 receptors in patients with mCRC. With this study, we wanted to highlight the importance of LPT as a prognostic and predictive marker, as well as to examine the importance of overexpression of HER2 in patients with mCRC. Methods: This research included 181 patients with KRAS wild type mCRC, who received anti EGFR therapy at the Oncology Institute of Vojvodina. 101 patients had a tumour of the left colon, 80 patients had a tumour of the right colon. The research analysed pathohistological and molecular characteristics of the tumour (KRAS, HER2) that were correlated with respect to the localization of the primary tumour. It also investigated the effect of anti-EGFR antibody therapy using progression-free survival (PFS) and overall survival (OS), in relation to the localization of the primary tumour, as well as in relation to HER2-receptor overexpression in patients with KRAS wt mCRC. Results:K RAS wt KLK was present in 101 patients (55.8%), KDK in 80 (44.2%). The median OS in patients with KLK was statistically significantly better (43 vs. 33 months, Mantel-Cox p= 0.005; Breslow p = 0.001). Median (PFS) with KLK was statistically significantly better than in patients with primary tumour localized on the right side (6 vs. 3 months, Mantel-Cox p <0.001; Breslow p < 0.001). Multivariate analysis of independent predictors of cumulative survival (OS) of patients with colorectal carcinoma: mucinous adenocarcinoma (p <0.001; HR 2.69; 95% CI 1.59-4.56), right localization (p = 0.022; HR 1.46; 95% CI 1.06-2.01), presence of perineural invasions (p = 0.034; HR 1.43; 95% CI 1.03-1.98) and the presence of tumours at the resection margin (p = 0.049; HR 1.6; 95% CI 1.02-2.81). Cox regression analysis, Conditional Forward method obtained independent predictors of cumulative progression-free survival (PFS) of patients with colon cancer: mucinous adenocarcinoma (p = 0.001; HR 2.53; 95% CI 1.49-4.29) and right localization (p = 0.004; HR 1.60; 95% CI 1.16-2.21). In the group of patients with KLK, Cox regression analysis, Conditional Forward metho, obtained only one independent predictor of cumulative survival (OS) and that is the presence of perineural invasion (p = 0.038; HR 1.60; 95% CI 1.03-2,48). In the group of patients with KDK, Cox regression analysis, Conditional Forward method, obtained only one independent predictor of cumulative survival (OS) and that is mucinous adenocarcinoma (p = 0.038; HR 3.12; 95% CI 1.72-5.66). The OS of patients with HER2 positive result 3+ is worse than that of patients with HER2 negative result (0,1+, 2 +) (p = 0.339). The PFS of patients with HER2 positive results was statistically significantly worse (p <0.001) compared to patients with HER2 negative results (despite the extremely small number of patients with HER2 positive results). Conclusion: Localization of the primary tumour is an important prognostic and predictive marker in the treatment of patients with wildtype mCRC with anti-EGFR antibodies. Patients with KDK have a statistically significantly shorter time to disease progression to anti-EGFR therapy and overall survival. The role of HER2 receptor overexpression in wild-type mCRC requires further examination, although we noted a low percentage of HER2 receptor overexpression in wt mCRC; these patients also had a shorter time to disease progression to anti-EGFR therapy and overall survival.