Colorectal cancer (CRC) worldwide belongs to one of the most frequent cancers affecting both genders. Surgery and 5-fluorouracil-based adjuvant chemotherapy are recommended for patients with high-risk stage II and stage III colon carcinoma. Mutations of genes encoding for specific proteins may have an impact on the time to recurrence. These proteins act over specific signaling pathways, are implicated in metabolic processes and regulate the cell cycle. Though many retrospective studies show strong associations between genetic mutations and the clinical outcome of patients with CRC, currently no validated biomarkers are used in clinical routine settings. Therefore, large prospective validation studies should be carried out in order to strengthen the position of genetic mutations in personalized treatment of patients with CRC.