ObjectiveOriginally described by Werth in 1884, controversy still exists as to the origin, nature, and pathogenesis of pseudomyxoma peritonei. The major theories include 1) chronic spillage of the mucinous epithelium from the primary tumor leading to multiple sites of implantation; or the alternative theory 2) independent origin of the tumors. To date, the available information regarding these issues is based on clinical observation, light microscopic analysis of tissue, cytologic specimens, and more recently, immunohistochemical data. The current study utilizes chromosomal analysis of multiple tumor sites in two cases of patients with this entity to provide additional insight to this controversial issue.Materials and MethodsUsing a method of cell culture without cell disassociation in combination with standard cell culture techniques, the authors performed cytogenetic analysis on several tumor sites derived from two patients with pseudomyxoma peritonei.ResultsTwo cases are reported. In both, tumor involved the ovaries, appendix omentum, as well as visceral and parietal peritoneal surfaces. Both showed borderline mucinous ovarian tumor and similar lesions in the appendix and peritoneum. Chromosomal analysis of multiple tumor sites in the first case showed a characteristic feature of each tumor site being an extra metacentric chromosome identified as 3. In the second case, evidence of instability of chromosome 5 was identified in all tumor sites. Monosomy of chromosome 15 was shared by the right ovary and appendix. The appendix demonstrated multiple additional anomalies as well.ConclusionThe data point to the theory of unifocal origin of this disease and the potential of these tumors to evolve chromosomally. Additional studies will be necessary to determine whether visible changes in the chromosomal composition are predictive of origin, evolution, and characteristics of pseudomyxoma peritonei.