As for the detection of EGFR activating and resistance mutations, LB can hold specific indications and advantages compared to a tissue biopsy (Table 1). Thus, this approach is non-invasive, can be repeated easily and can be an alternative to tissue analysis for an ALK rearrangement. In fact, an analysis using blood can be first performed when a tissue biopsy cannot be performed (in the case of the presence of a non-biopsiable tumor site and if the patient is fragile), when the percentage of tumor cells in a tissue biopsy is too small and/or when the amount/quality of biopsy tissue is insufficient (inadequate fixation used, hypo- or hyper-fixation, cell flattening or presence of an extensive zone of necrosis). Within the context of follow-up of patients receiving targeted therapy, LB holds several advantages compared to tissue biopsy. During tumor progression of fragile patients, this non-invasive approach can investigate persistent rearrangement or detect resistance mutation onset in the ALK gene and thereby treatment can be adapted with respect to the observed mutation. After a change in the treatment, renewed LB can be again performed at different times to look for the appearance of new mutations of the ALK gene. Monitoring of patients treated with crizotinib or alectinib can also be done by liquid biopsy. The persistence or reemergence of an ALK rearrangement can indicate the absence of response to treatment or can predict radiological progression before the appearance of clinical symptoms.