Long non-coding RNAs are now appearing from the genome’s dark matter. Much of what was previously labeled as junk DNA in fact produces non-coding RNA. While non-coding RNAs serve important biological functions, the lack of protein products requires new tools for detection and quantification. To meet this need, Stellaris RNA FISH probes from Biosearch Technologies are now entering laboratories around the world, allowing scientists to expand our understanding of the role of non-coding RNA and to pave the way for future diagnostic and prognostic tests. Here we address the challenges present in designing such probes against long non-coding RNA targets.