Molecular beacons composed of the artificial serinol nucleic acid (SNA) have demonstrated utility as novel fluorescence probes for visualization of RNA in fixed cells using both conventional fluorescence in situ hybridization (FISH) and wash-free FISH protocols. The SNA molecular beacons have higher affinity for target RNA and greater sensitivity than molecular beacons composed of DNA. Here we describe facile synthesis of the SNA using a conventional DNA synthesizer and protocols for purification by PAGE and HPLC as well as methods for use of the SNA molecular beacon in FISH.