Screening for cell-free DNA usually referred to as liquid biopsy holds great promise in cancer diagnosis and treatment. This article presents the results of the analysis of somatic tumor-specific mutations in circulating free DNA (cfDNA) isolated from the blood plasma of patients with stages I–IV colorectal cancer, based on the use of wild-type blocking allele-specific real-time polymerase chain reaction. This technique was specially designed for the analysis of biological specimens containing small amounts of mutant circulating tumor DNA. The study included 46 patients (18 female and 28 male participants) between 48 and 86 years of age (mean age was 67.1 ± 8.8 years). All patients underwent surgical treatment (radical surgery was performed on 85 % of the participants). Besides the molecular genetic analysis of cfDNA isolated from the blood plasma, standard histological staining was performed. Patients’ blood samples were collected before the surgery and on day 5 after it to test for KRAS and BRAF mutations. The applied PCR technique proved to be effective in detecting mutations in the RAS genes in stages II–IV of the disease, its sensitivity threshold being 0.1 %. Analysis of cfDNA before and after surgery may provide additional information on the surgical treatment outcome, development of new metastases, or presence of those previously overlooked. Wild-type blocking allele-specific real-time PCR is awaiting further validation in different clinical situations.