Dear Editor, Non-small cell lung cancer (NSCLC) accounts for over 75% cases of lung cancer, the leading cause of cancer deaths in the world. Most NSCLC patients are diagnosed at an advanced stage due to the inadequate screening program and late onset of clinical symptoms, leading to poor prognosis. 1 Discovery of accurate and sensitive biomarkers is in urgent need. Recently, circular RNAs (circRNAs) are emerging as a novel biomarker because of their conservation, abundance, cell type-specific and tissue-specific expression, and their roles in disease progression. 2, 3 Increasing studies focus on molecular mechanisms of NSCLC with fusion genes, a hybrid of two otherwise-separated genes caused from aberrant chromosomal translocations. The fusion gene Echinoderm Microtubule-associated protein-Like 4 (EML4)-Anaplastic Lymphoma Kinase (ALK) is present in 4% to 5% of NSCLC cases and generates oncogenic activity by activating ALK kinase. 4 Recently, mounting evidence demonstrates that fusion genes not only encode fusion proteins involved in tumorigenesis, but also generate non-coding RNAs contributing to tumor progression. For example, the circRNA generated by the MLL/AF9 fusion gene (fcircM9) in leukemia exerts pro-proliferative and pro-oncogenic activities, 5 prompting us to investigate whether the EML4-ALK fusion gene produces circRNA with clinical relevance in NSCLC. Unlike linear RNAs, circRNAs have a circular covalently-bonded structure, which endows circRNAs with higher tolerance to exonuclease digestion and prolonged lifetime in systemic circulation. CircRNAs are demonstrated to be enriched and stable in exosomes of peripheral blood. 6 Compared to traditional biopsy biomarkers in tumor tissues, circRNAs in body fluids could be used as more convenient and non-invasive “liquid biopsy” biomarkers to detect tumor at early and late stages. Here, we report a novel circRNA named as F-circEA generated from the EML4-ALK fusion gene by back-splicing and identify its role in promoting tumor development. Notably, the existence of F-circEA in plasma suggests that F-circEA is a potentially novel “liquid biopsy” biomarker for diagnosis of EML4-ALK-positive NSCLC, guiding targeted therapy in clinic.