- The discovery and functional analysis of noncoding RNA (ncRNA) systems in different organisms motivates the development of tools for aiding ncRNA research. Several tools exist that search for occurrences of a given RNA structural profile in genomic sequences. Yet, there is a need for an “RNA BLAST” tool, i.e., a tool that takes a putative functional RNA sequence as input, and efficiently searches for similar sequences in genomic databases, taking into consideration potential secondary structure features of the input query sequence. This work aims at providing such a tool. Our tool, denoted StemSearch , is based on a structural representation of an RNA sequence by its potential stems. Potential stems in genomic sequences are identified in a preprocessing stage, and indexed. A user-provided query sequence is likewise processed, and stems from the target genomes that are similar to the query stems are retrieved from the index. Then, relevant genomic regions are identified and ranked according to their similarity to the query stem-set while enforcing conservation of cross-stem topology. Experiments using RFAM families show significantly improved recall for StemSearch over BLAST , with small loss of precision. We further demonstrate our system’s capability to handle eukaryotic genomes by successfully searching for members of the 7SK family in chromosome 2 of the human genome. StemSearch is freely available on the web at: http://www.cs.bgu.ac.il/ ∼ negevcb/StemSearch .