Expression of HLA G may be a way for tumor cells to escape immuno‐surveillance. HLA G is selectively expressed by extravillous trophoblast in the human placenta, a tissue that does not express HLA A or B molecules. It is tempting to propose that tumor cells resemble this unique HLA class I phenotype as they frequently lose classical HLA A, B and C class I expression. Such peculiar HLA class I distribution would in theory allow tumor cells to escape from T‐ and NK‐cell cytotoxicity. To determine whether HLA G is expressed on tumor cells, we studied HLA G mRNA levels using RT‐PCR and HLA G cell‐surface expression by immuno‐histological techniques in a panel of 50 human solid tumor tissues, 31 tumor cell lines of different origin, 4 autologous mucosa samples and 3 peripheral white cell samples. We found mRNA transcripts of different HLA G isoforms in most of the samples studied. However, we did not detect cell‐surface expression of HLA G using 3 specific monoclonal antibodies (MAbs; 87G, 01G and G223). HLA G was detected only in the U937 myelomonocytic cell line after stimulation with IFN‐γ. We favor the hypothesis that HLA G plays a minor role, if any, in providing an inhibitory signal to NK cells to escape immunosurveillance. We cannot, however, exclude the possibility that some other HLA G isoforms may be expressed in some tumors. Int. J. Cancer 81:512–518, 1999. © 1999 Wiley‐Liss, Inc.