The technology of exon trapping, sometimes called exon amplification, strives to exploit the phenomenon of mRNA splicing to discover genes directly from genomic DNA. There are three distinct exon trapping methodologies that differ simply in the genomic target of interest. The original experimental design was to capture isolated 3′-splice sites residing within fragments of genomic DNA (1), whereas later approaches focused on either complete internal exons (2–5) or entire 3′-terminal exons (6). The requirement of complete, intact exons as targets has proven absolutely essential, and only the trapping of complete internal or 3′-terminal exons is practical.