Purpose: The presence of similar histologic subtypes of epithelial ovarian and enclometrial cancers has long been noted, although the relevance of this finding to pathogenesis and clinical management is unclear. Despite similar clinical characteristics, histologic subtypes of cancers cif the ovary and endometrium are treated according to organ of origin. This study compares the gene expression profiles of analogous histologic subtypes of cancers of the ovary and eneometrium using the same genomic platform to determine the similarities and differences between these tumors. Experimental, Design: Gene,expression profiles of 75 cancers (endometrioid, serous, and clear cell) of the ovary and endometrium, five renal clear cell cancers, and seven normal epithelial were determined using a 11,000-element cDNA array. All images were analyzed using BRB ArrayTools. Validation was done using real-time PCR on select genes and immunohisto-chemical staining. Results: Comparison across enclometrial and ovarian cancers and serous and endometrioid tumors showed expression patterns reflecting their organ,of origin. Clear cell tumors, however, showed remarkably similar expression patterns regardless of their origin, even when compared with renal clear cell samples. A set of 43 genes was common to comparisons of each of the three histologic subtypes of ovarian cancer with normal ovarian, surface epithelium. Conclusions: The comparison of the gene expression profiles of endometrioid and serous subtypes of ovarian and enclometrial cancer are largely unique to-the combination of a particular subtype in a specific organ. In contrast, clear cell cancers show a remarkable similarity. in gene expression profiles across organs (icluding kidney) and could not be statistically distinguished.