Circulating tumour DNA (ctDNA) is a novel tool that has been investigated in several types of tumours, including colorectal cancer (CRC). In fact, the techniques based on liquid biopsies are proposed as appealing non-invasive alternatives to tissue biopsy, adding more insights into tumour molecular profile, heterogeneity and for cancer detection and monitoring. Additionally, some analysis showed that in CRC patients, ctDNA seems to act as a biomarker able to predict the outcome (prognostic role) and the response to treatments (predictive role). In particular, in the early stage CRC (stage I-III), it could represent a time marker of adjuvant therapy as well as a marker of minimal residual disease and recurrence risk in addition to the already recognized risk factors. In metastatic CRC, the analysis of molecular tumour profile by ctDNA has shown to have high concordance with the tissue biopsy at diagnosis. Additionally, some studies demonstrated that ctDNA level during the treatment was linked with the early response to treatment and prognosis. Finally, the quantitative analysis of ctDNA and copy number alterations may be useful in order to detect resistance to therapy at the time of progression of disease and to help in finding new therapeutic targets.