Ovarian carcinoma can arise synchronously from multiple independent sites and metastasize widely. Therefore, it is frequently unclear whether bilateral tumors represent two independent primaries or one primary and a metastasis. We have used X chromosome inactivation of the androgen receptor gene and microsatellite instability at four chromosomal loci to evaluate the clonal origin of 39 bilateral ovarian carcinomas. An identical monoclonal pattern was found bilaterally in all cases including 10 stage I bilateral ovarian carcinomas. Microsatellite alterations were identified in three cases, and in all three, identical alterations were present in tumor tissue from both ovaries. These results suggest that bilateral ovarian carcinomas evolve as unifocal neoplasias and that metastatic dissemination can occur early in the course of the disease.