In the context of pregnancy, several immunomodulating mechanisms have developed to regulate the maternal immune response to its semiallogeneic fetus. The nonclassical major histocompatibility complex class I human leukocyte antigen-G (HLA-G) was suggested to be involved in these mechanisms due to its unique features and its immunosuppressive abilities. We have previously described the presence of HLA-G complexes at the cell surface, which confer an efficient natural killer inhibition through the leukocyte Ig-like receptor-1 (LIR-1). We further demonstrated the presence of HLA-G free heavy chain (FHC) complexes, which are not recognized and possibly interfere with LIR-1 and HLA-G interaction. Here we expand our understanding of the nature of the complexes by demonstrating that these complexes are observed mainly on the cell surface and not inside the cell. We further determine that the HLA-G stability at the cell surface is not a direct result of the presence of the HLA-G complexes. Finally, we suggest that the FHC complexes are probably assembled from the conformed complexes present on the cell surface.