Mincle family receptors bind oligosaccharide ligands through extracellular carbohydrate-recognition domains (CRDs) and initiate intracellular signalling by interacting with the common Fc receptor γ subunit (FcRγ). Mincle and dectin-2 stimulate macrophages in response to pathogen binding, while blood dendritic cell antigen 2 (BDCA-2) modulates cytokine production. The oligomeric states of these mincle family receptors and the orientations of their CRDs have been investigated to elucidate how extracellular ligand binding initiates cytosolic signalling. Chemical crosslinking and introduction and deletion of cysteine residues have been used to show that dimers of mincle in transfected mammalian cells are stabilized by disulfide bonds between cysteine residues in the neck sequence that links the CRD to the membrane. BDCA-2 forms noncovalent dimers in the absence of a neck-region cysteine residue, although a naturally occurring variant can form an interchain disulfide bond. Cysteine residues in the transmembrane portions of these receptors do not form disulfide bonds and are not required for dimer formation or association with FcRγ, but may facilitate trafficking to the cell surface. To investigate how CRDs are positioned in receptor dimers, bacterial expression systems were developed to produce extracellular domain dimers. Fusion to N-terminal dimerization domains in place of the transmembrane domain was used to improve dimerization efficiency. This approach was used to create disulfide-linked mincle extracellular domain dimers and noncovalently linked extracellular domain dimers of dectin-2 and BDCA-2. Analysis of these constructs, as well as existing crystal structures of the CRDs from these proteins and extended versions of the extracellular domain of BDCA-2, showed that there is only limited interaction of the CRDs in the dimers, but interactions can be stabilized by the presence of the neck region. The resulting orientation of sugar-binding sites in the dimers would favour crosslinking of multiple dimers by oligosaccharide ligands, causing clustering of FcRγ to initiate signalling.