The non-classical human leukocyte antigen (HLA)-G plays a crucial role in the induction of tolerance at the feto-maternal interface as well as in transplantation, cancer, inflammation, and autoimmune diseases. To understand gene regulation and the impact of polymorphic sites on the function, simple and easy feasible approaches are needed for the detection of HLA-G variants in coding and non-coding regions. Here we summarize a set of methods for the identification of variants in the exon 2-4, in the 3' untranslated region and in the gene promoter region of the HLA-G gene.