Most melanocytic tumors can be characterized as a benign nevus or a melanoma by a trained pathologist using traditional histopathological methods. However, a minority demonstrates ambiguous features and continues to be a diagnostic challenge. Genetic expression profiling (GEP) assays have been developed in an effort to resolve this dilemma. These assays measure mRNA levels of specified genes using reverse transcription quantitative polymerase chain reaction technology. The development of GEP assays, methodology, challenges associated with GEP validation and testing, and the suitability of a currently available GEP test for clinical use are reviewed.