Metastatic prostate cancer remains a prevalent disease in the United States that requires detailed characterization of its pathobiology. In the December 2004 issue of Cancer Research, a comprehensive study by Shah et al. demonstrated that metastatic androgen-independent prostate cancer is a collective group of diseases even within the same patient. Understanding the molecular and phenotypic determinants of this heterogeneity is essential in assessing therapeutic outcomes in the management of prostate cancer progression.