Translocations and inversions affecting FGFR2 have been detected in several solid tumors, including e.g. breast cancer, lung cancer, and the intrahepatic subtype of cholangiocarcinoma. Several partner genes have been described to be fused to FGFR2 after rearrangement. The resulting fusion genes are predicted to encode chimeric proteins carrying the kinase domain of FGFR2. Most of the currently known FGFR2 fusion products are likely to exhibit oligomerization capability resulting in kinase activation. In prostate cancer FGFR2 was found to be fused to the promoter region of SLC45A3 predicted to result in signal activation by overexpression of the FGFR2 protein. Recent studies indicate the involvement of FGFR2 fusion proteins in tumorigenesis. Moreover, in vitro studies suggest that certain FGFR tyrosine kinase inhibitors may provide a new therapeutic option for patients showing FGFR2 rearrangement. Hence, detection of FGFR2 rearrangements using ISH may help to identify patients which might respond to FGFR2 kinase targeting therapies.