The colorectal cancer (CRC) modern therapy is using adjuvant and neoadjuvant companion therapeutic agents, part of them having an anti-angiogenic action. Their benefic effect can be annulated by some gene mutations, which are interfering in signal transduction pathways. One of the more frequent activating mutations is occurring in the KRAS gene. We assessed the KRAS mutations by two molecular methods, in a group of patients with a follow-up until 144 months, aiming to establish eventual correlations between the presence of mutations and the evolution of patients. We tried to appreciate the prognostic value of these mutations. A retrospective study was conducted on 74 patients treated by radical surgery; the surgical specimens were analyzed macroscopically and the histopathological type and degree were established. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and pyrosequencing were performed on paraffin-embedded tumor specimens. Statistical analysis showed significant differences in survival between patients with wild type gene and patients with mutation in codon 13; the same results were also obtained regarding TNM I, II stages or Dukes type A and B cases. However, for the patients in stage IV pTNM, the evolution was slightly better in association with a KRAS mutation than in wild type cases.