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Over the past decade, microarray technology has become a powerful tool to provide a genome-wide view of genetic or epigenetic changes associated with tumor metastasis. To extract biologically meaningful information from the vast amounts of microarray data, it is crucial to choose suitable biological systems and have vigilant experimental design. In this review, I will discuss several experimental systems that are used to identify genes involved in tumor metastasis by microarray analysis. Also highlighted are the pros and cons for each system. In particular, I will describe our experience of using microarray technology to identify the transcription factor Twist as an essential player in tumor metastasis.