Metastasis is a multistep process that represents the final stage in cancer progression and heralds a terminal disease state. Understanding the molecular changes required for the establishment of metastases that are common or specific to a particular location and the corresponding changes in the host tissue response that may support metastasis formation is highly relevant for the cancer management. To address metastatic tumor gene expression, I used a multistage prostate carcinogenesis model and performed affymetrix microarray analysis of laser capture microdissected tumor cells in liver, lung and kidney tissues as well as in primary tumor. By comparing metastatic gene expression profiles with those of the primary tumor, I found candidate genes for organ specificity and a small set of genes shared by metastases at all three locations. These common genes may be relevant to the metastatic process itself, and will require further investigation. To address the host-response gene expression profile to metastatic growth, I performed affymetrix microarray analysis of microdissected liver microenvironment in direct contact with macrometastases and as well of the healthy liver. Comparison of these two microenvironments revealed genes related to a reactive inflammatory response surrounding metastases that may potentially support their growth. The distinct signatures uncovered provide potential clues as to some of the requirements for metastatic establishment and growth where both tumor cells and the surrounding microenvironment play an important role, and open possibilities for future functional analysis and, hopefully, clinical applications