Assessment of molecular heterogeneity in tumors is a challenging task. Palanisamy et al have demonstrated the novel existence of a rare subset of prostate cancer with heterogeneous molecular aberrations involving ETS family genes and SPINK1 expression utilizing both standard immunohistochemistry (IHC) and RNA in situ hybridization (Advanced Cell Diagnostics RNAscope™ Technology). The presenter will discuss the application of RNA ISH technology to reveal previously unidentified molecular subtypes of prostate cancer.