The HistoCheck webtool provides clinicians and researchers with a way of visualizing and understanding the structural differences among related major histocompatibility complex (MHC) molecules. In the clinical setting, human leukocyte antigen (HLA) matching of hematopoietic stem cell donors and recipients is essential to minimize ‘‘graft versus host disease’’ (GvHD). Because exact HLA matching is often not possible, it is important to understand which alleles present the same structures (HLA–peptide complexes) to the T-cell receptor (TCR) despite having different amino acid sequences. HistoCheck provides a summary of amino acid mismatches, positions, and functions as well as 3-dimensional (3D) visualizations. In this chapter, we describe how HistoCheck is used and offer advice in interpreting the query results