Differential Display between metastasizing and non-metastasizing human melanoma cell lines NMCL-1 and 530 led to the identification of a putative transmembrane receptor, designated as THW, which is down-regulated in the metastasizing cell line. THW is composed of 193 aa, exhibits four putative transmembrane domains and does not reveal any homology to other proteins. Down-regulation of THW is correlated with metastatic capacity of melanoma cell lines. THW was down-regulated in mammary carcinoma cell lines compared with cell lines derived from non-malignant mammary epithelium, in pancreas cell lines derived from metastases compared with a cell line derived from a primary tumor and in several tumor tissues compared with normal tissues. The function of THW as a tumor suppressor is emphasized by the location of the THW gene on chromosome 6q. LOH for this region has been reported in malignant melanoma and prostate, pancreas, uterine and mammary carcinomas.