One of the most fundamental biological processes in development, as well as a primary mechanism for tumor metastasis, is epithelial–mesenchymal transformation (EMT). To gain a greater understanding of this transition, we have obtained a genomic profile of the critical stages before and during this rapid change in morphology in the developing mouse palate. By isolating the medial edge epithelium of each palatal shelf, we were able to obtain pure gene expression data without contamination from surrounding mesenchymal cells. Our results support the important role of the TGF-β/Smad signal transduction pathway in the stimulation of EMT by means of up-regulation of the EMT-inducing gene, LEF-1. We document changes in gene expression profiles during palatal adherence and subsequent transformation of the medial edge epithelial seam that suggests a high number of LEF-1 target genes promote cellular transformation to mesenchyme. These include genes involved in cell adhesion, polarity, cytoskeletal dynamics, migration, and intracellular signaling. This knowledge of the changes in gene expression levels during palatogenesis should lead to a better understanding of the mechanisms of EMT. Developmental Dynamics 234:132–142, 2005. © 2005 Wiley-Liss, Inc.