Gene rearrangements that involve NTRK1/2/3 can generate fusion oncoproteins that contain the kinase domains of TRKA/B/C, respectively. In NSCLC, NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1%. The TRK inhibitors namely, Larotrectinib (LOXO-101) and Entrectinib (RXDX-101) are oral tyrosine kinase inhibitor that have high selectivity and potency for TRKA, TRKB, and TRKC. The detection of NTRK1/2/3 translocations by Fluorescence in situ Hybridization (FISH) may be of diagnostic and therapeutic relevance.