X-ray crystallographic and cryo-EM structural analyses have been performed on the same chromatographic fraction of quinol-dependent nitric oxide reductase from Neisseria meningitidis to high resolution. This represents one of the first examples in which the two approaches have been used to reveal a monomeric assembly in the crystal and a dimeric assembly in the frozen cryo-EM solution. A number of factors have been identified that may trigger the destabilization of the helices that are necessary to preserve the integrity of the dimer.