The nuclear matrix is the structural component of the nucleus that determines nuclear morphology and organizes the DNA in a three-dimensional fashion that is tissue specific. Previously, some of the nuclear matrix proteins have been reported to be both tissue and cell type specific and are altered with the state of differentiation and transformation. This study demonstrates that the nuclear matrix is specific for the individual lobes of the normal rat prostate and that the nuclear matrix undergoes changes in protein composition in the Dunning prostate cancer tissue. Additionally, in the Dunning rat prostate adenocarcinoma cell lines, there is a range of tumor phenotypes and the nuclear matrix varies in composition in each tumor cell type. These differences in the nuclear matrix proteins are associated with quantitative changes in nuclear morphology that form the pleiomorphic state of the cancer nucleus.