Free plasma DNA is routinely used to analyze mutations in EGFR in patients with advanced stage lung cancer. In contrast, plasma RNA is not used routinely, or very rarely used, for detection of EML4-ALK rearrangements. Nonetheless, the detection of this genomic alteration can be performed with plasma using the reverse transcription-polymerase chain reaction (RT-PCR). While in theory this approach can detect an ALK rearrangement in the blood of patients shown to be ALK positive after analysis of a tissue biopsy, it still has some limits. The first hurdle concerns mastering of the pre-analytical delay between the blood sampling and the extraction of the plasma RNA, knowing that the blood RNA degrades rapidly after sampling. The addition of a solution such as Trizol or immediate plasma freezing at low temperature (minimum of −80 °C) allows better conservation of the integrity of the plasma RNA. In practice, this is not always possible to do in clinical routine. The second hurdle is the low detection limit of the EML4-ALK rearrangement by RT-PCR (around 20–25%), which also limits its use in daily practice .