By screening for differentially expressed genes in cancer cells, using the RNA differential display (DD) technique, we identified a novel cDNA, LDOC1, that is down-regulated in some cancer cell lines. A Northern blot analysis revealed no expression in pancreatic and gastric cancer cell lines but ubiquitous expression in normal human tissues. This new gene was mapped on chromosome Xq27 and the predicted protein sequence showed no similarity to known sequences in the database except for a leucine zipper-like motif at the N-terminal region and a proline-rich region that shares marked similarity to an SH3-binding domain. In an enhanced green fluorescent protein (EGFP) assay, the EGFP-LDOC1 fusion protein was localized in the nucleus. Although the function of LDOC1 is still unknown, our results suggest that this novel gene codes for a nuclear protein, and down-regulation of LDOC1 may have an important role in the development and/or progression of some cancers.