The chromosomal constitutions of three murine cell lines that developed in vitro from tumors that grew in nude mice after orthotopic and ectopic injections of three human prostate tumor cell lines were examined by histopathology, conventional G-banding, and with fluorescence in situ hybridization techniques. All three murine cell lines showed unique marker chromosomes involving mouse chromosome 12, with a common break point. Histopathologic evidence from a murine prostate gland into which SP 3031 cells had been injected indicated dysplastic glandular epithelium and carcinomatous areas. These observations further indicate that: (a) human prostate tumors are capable of transforming host organ cells, (b) host cells have specific chromosomal alterations that may be associated with transformation, and (c) the process of host cell transformation can be demonstrated in histological sections. Although cancer cell heterogeneity and drug-resistant phenotypes are caused by additional genetic alterations and clonal evolution of the original tumor, transformation of the host's distant organ cells may also contribute because most therapies are directed only to the original cancer cells.