The HLA-G molecule has been implicated in the escape from the host antitumor immune response. Besides, this molecule appears also to be detected in transplant recipient's tissues, mainly those with fewer rejection episodes. Since skin carcinomas develop frequently in organ transplant recipients, we asked whether HLA-G could be expressed in these lesions, therefore allowing tumor development in such patients. Immunohistochemical analysis of kidney transplant recipients presenting various types of epithelial malignant tumor and benign cutaneous lesion was done using a specific anti-HLA-G antibody. HLA-G was expressed in 35% of specimens of SCC, 47% of in situ carcinoma, 27% of AK and 14% of BCC but never in the 24 benign lesions studied. Many benign specimens were obtained from the same patients who had tumors, demonstrating that HLA-G expression was restricted to the malignant sites. Interestingly, HLA-G was expressed by proliferative keratinocytes, inflammatory infiltrates and even endothelial cells. Cytokines triggered in the course of organ transplantation include IL-10. This molecule may induce expression of HLA-G, which in turn may be implicated in tumor development in transplanted recipients. © 2003 Wiley-Liss, Inc.