Oligonucleotide microarrays were used to profile and compare gene expression patterns between uterine serous papillary carcinoma and ovarian serous papillary carcinoma or normal endometrial epithelial cells. mRNA fingerprints readily distinguish the more biologically aggressive and chemotherapy resistant USPC from OSPC or NEC. Plasminogen activator inhibitor is the most highly up-regulated gene in OSPC relative to USPC, whereas the c-erbB2 gene product (HER-2/neu) is strikingly overexpressed in USPC relative to OSPC and may therefore represent a novel diagnostic and therapeutic marker for this highly aggressive subset of endometrial tumors.