The SIRP family of myeloid-paired receptors are characterized by having both activating and inhibiting members with extracellular regions that are relatively similar. Making good reagents to these receptors is not straightforward, particularly as they are relatively polymorphic. We describe the production of a monoclonal antibody (MAb) called OX130 that recognizes both common alleles of the human activating SIRPβ1 receptor but also cross-reacts with one of the common alleles of the inhibitory human SIRPα receptor. Thus one might get different outcomes when this MAb is used in assays from different individuals and shows the importance of characterizing SIRP MAb in this way.