AimsThe majority of pancreatic ductal adenocarcinomas (PDACs) harbour oncogenic mutations in KRASwith variants in TP53, CDKN2Aand SMAD4also prevalent. The presence of oncogenic fusions including NTRKfusions are rare but important to identify. Here we ascertain the prevalence of NTRKfusions and document their genomic characteristics in a large series of PDAC.MethodsWhole genome sequencing and RNAseq were performed on a series of patients with resected or locally advanced/metastatic PDAC collected between 2008 and 2020 at a single institution. A subset of specimens underwent immunohistochemistry (IHC) analysis. Clinical and molecular characterisation and IHC sensitivity and specificity were evaluated.Results400 patients were included (resected n=167; locally advanced/metastatic n=233). Three patients were identified as harbouring an NTRKfusion, two EML4-NTRK3(KRAS-WT) and a single novel KANK1-NTRK3fusion. The latter occurring in the presence of a subclonal KRASmutation. Typical PDAC drivers were present including mutations in TP53and CDKN2A. Substitution base signatures and tumour mutational burden were similar to typical PDAC. The prevalence of NTRKfusions was 0.8% (3/400), while in KRASwild-type tumours, it was 6.25% (2/32). DNA prediction alone documented six false-positive cases. RNA analysis correctly identified the in-frame fusion transcripts. IHC analysis was negative in the KANK1-NTRK3fusion but positive in a EML4-NTRK3case, highlighting lower sensitivity of IHC.ConclusionNTRKfusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing for KRASmutations and subsequent RNA-based screening could help identify these cases in PDAC.