The NTRK3 gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. Infantile fibrosarcoma (IFS) is a soft-tissue sarcoma that arises in the first year of life and is the most common non-rhabdomyosarcoma in this age group. Classically, IFS is driven by the t(12;15)(p13;q25) translocation encoding the ETV6–NTRK3 fusion protein.