DNA microarray technology is a powerful tool for genome-wide gene expression analysis of biological samples including skin and epidermal keratinocytes. Here we review the methodology for expression profiling analysis of skin tissue or purified keratinocytes from mice. We explained the methodology and protocols for RNA preservation and purification, RNA quality and integrity tests, and DNA microarray technology types that can be used. Furthermore, using a data set of mice samples, we explained how to perform chip raw data preprocessing and normalization, differential expression analysis, gene-clustering and functional analysis of gene deregulation.