This article contains an original 5E lesson plan developed from conservation genetics research on the giant North American hellbender salamander, Cryptobranchus alleganiensis alleganiensis. The lesson plan provides background information on the hellbender, reviews basic genetics, and exposes students to the scientific process that is used during PCR (polymerase chain reaction) and the analysis of microsatellites in order to calculate allele and genotype frequencies for understanding genetic variability. Once completing the lesson, students should make the connection between molecular research and conservation of a rare, cryptic, and interesting species.