Dimerization of epidermal growth factor receptor (EGFR/ErbB) homologs is necessary for their activation. Dysregulation of each of these receptors is linked to a variety of cancers. Most members of this protein family adopt a tethered conformation in the absence of ligand that prevents the formation of active dimers, while ErbB2 adopts a constitutively extended conformation mimicking the ligand-bound conformation. Surprisingly, ErbB2 does not homodimerize yet is the preferred dimerization partner of the other EGFR homologs. The reasons for this are unclear, and previous attempts to address these questions using structural techniques were unsuccessful. Here we drove dimerization of the extracellular domains of EGFR family members with ErbB2 by fusion of one extracellular domain to the light and the other to the heavy chain of an antibody. We pursued crystallization of these heterodimers, and currently use small angle x-ray scattering and electron microscopy to determine the structure of these heterodimers in the presence and absence of ligand to reveal what structural facets underlie their activation.