NTRK1 encodes a tyrosine kinase (TK) receptor for the nerve growth factor (NGF). The NTRK1 gene was found to be rearranged in about 12% of papillary thyroid carcinoma (PTC) cases. PTC accounts for about 80% of all thyroid cancers. NTRK1 rearrangements result in the fusion of the 3‘ end of the NTRK1 gene with the 5‘ end of different activating genes (TPM3, TPR, or TFG). All these fusion genes encode hybrid proteins comprising the TK domain of NTRK1 and the N-terminus of the partner proteins carrying coiled-coil domains. NTRK1 rearrangements were shown to be involved in thyroid carcinogenesis. Several studies showed that NTRK1 rearrangements may be associated with a worse clinical course when compared with NRTK1 rearrangement-negative PTCs. Recently, NTRK1 rearrangements were also found in lung adenocarcinomas. Various inhibitors targeting the NTRK1-derived fusion proteins were shown in vitro to inhibit proliferation of cells expressing the fusion genes. This indicates that these fusion genes are potential therapeutic targets. Hence, detection of NTRK1 rearrangements by Fluorescence in situ Hybridization represents a useful tool for studying thyroid carcinogenesis and may be of prognostic and therapeutic significance.