Identification of genes that are upregulated in tumors, and whose normal expression excludes adult somatic tissues but includes germline and/or embryonic tissues, has resulted in a rich variety of cancer antigens that are attractive targets for cancer vaccine and other therapeutic approaches. In the present study, we extended this approach to include genes strongly and restrictively expressed in the placenta by mining publicly available SAGE and EST databases. We identified a number of genes with high expression in placenta and different cancer types but with relatively restricted expression in normal tissues. The gene with the most distinctive expression pattern was found to be PLAC1, which encodes a putative cell surface protein that is highly expressed in placenta, testis, cancer cell lines and lung tumors. Hence we have designated it CT92. We found by ELISA that PLAC1 is immunogenic in a subset of cancer patients and healthy women. Its physical and expression characteristics render it a potential target for both active and passive cancer immunotherapeutic strategies.