Rearrangements affecting the FGFR3 gene are frequently found in carcinomas of various types including multiple myeloma (MM), bladder cancer, glioblastoma, peripheral T-cell lymphoma, and lung squamous cell carcinoma. FGFR3 encodes for a transmembrane receptor tyrosine kinase which dimerizes after ligand binding leading to activation of downstream signaling cascades. This gene develops characteristic oncogenic activities after fusion to several gene partners which often leads to ligand-independent activation of the tyrosine kinase of the FGFR3 fusion protein. Several in vivo and in vitro studies have demonstrated the therapeutic potential of FGFR inhibitors in cell lines and animal models harboring FGFR3 fusion genes. Hence, the detection of FGFR3 translocations by Fluorescence in situ Hybridization may be a useful predictive biomarker in the selection of patients for FGFR-targeted therapy.