Tumors release components such as of cell-free DNA fragments (ctDNA, circulating tumor DNA) or viable cells (CTC, circulating tumor cells) into the circulation, which reflect their genetic or epigenetic landscape. Therefore, CTC and ctDNA can be used for molecular profiling and prognostication purposes for malignant diseases from blood and other body fluids. A liquid biopsy (LB) refers to the sampling and analysis of non-solid biological tissue, and therefore is a simple and minimal-invasive alternative to surgical biopsies. The LB holds great promise for precision and personalized medicine and in particular, ctDNA has been demonstrated to be a valuable tool to detect cancer recurrence, to predict tumor burden and treatment response, as well as to identify resistance mechanisms and the emergence of novel actionable targets has been proven in numerous studies summarized monitor recurrence, resistance, metastasis and minimal residual disease (1-4). Moreover, it has been shown that patients having higher ctDNA levels at certain time points, i.e. prior to therapy initiation, prior or after tumor resection had significantly shorter PFS (progression-free survival) and/or overall survival (OS). Furthermore, ctDNA levels can indicate recurrence of a tumor long before progression is clinically obvious and it was shown that the analysis of ctDNA is a better marker for the detection of recurrence of breast and colorectal cancer than conventional protein tumor markers (5, 6). A continuous monitoring of changing levels of ctDNA during initiation and maintenance of cancer therapy can be used to assess the patient´s response without burdening the patient, and more importantly progression can be detected before it is clinically obvious (7-9). Another attractive aspect of using ctDNA is the potential to infer the mechanism resistance that inevitably arise for almost all targeted therapies across all tumor entities (10-15). The potential of ctDNA is not limited to patients already suffering from cancer but it may also play a crucial role in the detection of pre-clinical cancer. However, very few studies have focused on the evaluation of ctDNA detection in early-stage cancers (i.e. stage I-II tumors) with even less data available on the detection of ctDNA in blood samples from pre-symptomatic cancer patients.