While immunohistochemistry has gained universal adoption in anatomic pathology over the last thirty years, RNA ISH has lagged behind due to its poor sensitivity and absence of automation. Recent advances in RNA ISH, specifically the RNAscope technology, have made the technique dramatically more sensitive in parallel to the development of automation on commonly used IHC/ISH stainers. As a result of these advances, RNAscope RNA ISH is becoming a valuable tool for the pathologist in the assessment of various markers across numerous specimen and disease types with straightforward chromogenic assays at the light microscope. This presentation will review the RNAscope technology and its applications in anatomic pathology including detection of SARS-CoV-2, albumin, and HPV.