Fibroblast Growth Factor Receptor 2 (FGFR2) is a family of the FGFR receptor tyrosine kinase and has two main splice isoforms, FGFR2b and FGFR2c expressed in normal epithelial and mesenchymal cells respectively. These two splice isoforms have different oncogenic roles which are highly context dependent. Epithelial-derived cancers express the oncogenic variant, FGFR2c isoform through a process of alternative splice isoform switching and this drives several hallmarks of cancer. Currently, FGFR2 isoform-specific antibodies are not available, and this hinders the prognostic, predictive and target therapy of FGFR2c in solid cancers. Recently, our laboratory optimised and validated BaseScope RNA in situ hybridisation (ISH) assay to detect the two splice isoform using ACD BIO customised exon junction specific probes. Furthermore, we have optimised a doublex BaseScope RNA ISH assay to detect the two FGFR2 splice isoforms in a single section to save precious patient tissue in the clinic. This talk covers the discovery of novel biomarkers of FGFR2 splice isoforms and their biology in the progression of endometrial cancers and other solid carcinomas. The presentation will also highlight the proof of concept on the translational significance of this novel assay from biomarker discovery to targeted personalised therapy in endometrial cancer.