Many detailed genetic studies have been reported on prostate carcinogenesis. A major shortcoming of these studies, however, is the fact that most data have been gained from investigations that were performed at a single point of time during tumor development. Only little is known on the dynamic process of genetic changes during the course of the disease. We performed comparative genomic hybridization in two cases of prostate cancer brain metastases. Tissue samples from the primary tumors, the locally recurrent tumor in one case, and the brain metastases from both cases were available for analysis. The number of chromosome abnormalities was found to be increased in the metastases. This contrasts to a remarkably stable chromosome composition of the primary tumor over several years, even in an androgen-depleted environment. When focusing on these changes, which either emerged as new common aberrations in both brain metastases, or which were commonly present in the primary and metastatic tumors, we were able to delineate five chromosomal sites that are assumed to be related to prostate cancer metastasis: 8q21 approximately q22, 8q24, 15q24 approximately q26, 20q12 approximately q13.1, and Xq12 approximately q21. These findings provide new evidence for a putative role of genes at 15q and 20q in the metastatic process of prostate cancer.