We have investigated the use of complementary DNA microarrays in revealing patterns of gene expression in low- and high-grade serous papillary ovarian carcinomas. We used frozen tumor samples from eight ovarian and three peritoneal serous papillary adenocarcinomas. We extracted total RNA from the samples using Trizol and used pooled RNA from two immortalized ovarian surface epithelial cell lines as a reference. Tumor and reference RNAs were amplified using a modified Eberwine method. Cy3 (reference) or Cy5 (samples) was used to label 4 μg of amplified RNA, and a 6,500-cDNA microarray chip was used to compare each sample to the reference. We observed a high degree of similarity in the gene expression profiles of low- and high-grade tumors. Forty-five outliers (fourfold up- or downregulated compared with the reference in all 11 samples) were identified. The overexpressed outliers included those encoding CTBP-1, Jun-D, MADCAM-1, and Wilms tumor zinc-finger protein. Genes showing reduced expression included those for IL-8, metallothionein 1X, CDC25B, and uteroglobin. We explored possible differences between the low- and high-grade samples by performing Wilcoxon analysis on each gene in the two groups. This step yielded 27 genes that were differentially expressed (P< 0.03) among all low- and high-grade cancers and were sufficient for separating them on multidimentional scaling. Many of the overexpressed genes may be used as tumor markers or serve as therapeutic age