Mucinous tumors of the ovary are often associated with mucinous tumors of the appendix. It has not been clearly determined whether they are independent or metastatic neoplasms. A clinicopathologic study and a comparative analysis of c-Ki-ras mutations were done in six cases of synchronous ovarian and appendiceal tumors. The clinicopathologic features (simultaneous presentation, bilaterality or right-sided predominance, similar histopathologic findings, presence of pseudomyxoma peritonei) suggested that they were primary appendiceal tumors metastatic to the ovaries. DNA was extracted from formalin-fixed, paraffin-embedded tissue, and target sequences were amplified in vitro by the polymerase chain reaction. Mutations were detected by the presence of restriction fragment length polymorphism, artificially introduced by the use of mutant amplimers. The pattern of c-Ki-ras mutations was identical in the ovarian and appendiceal tumors of all patients. Four patients had a GGT --> GAT (Gly --> Asp) transition and one a GGT --> GTT (Gly --> Val) transversion, all detected in codon 12. No mutation was found in the sixth patient in either the ovarian or the appendiceal tumor. Because c-Ki-ras mutations are considered to represent an early event in tumorigenesis, our results support a clonal nature for both tumors and suggest that they are not independent tumors but rather originate one from another.