Transthyretin (TTR), a 54 kDa homotetrameric protein that transports thyroxine (T4), has been associated with clinical cases of TTR amyloidosis for its tendency to aggregate to form fibrils. Many ligands with a potential to inhibit fibril formation have been studied by X-ray crystallography in complex with TTR. Unfortunately, the ligand is often found in ambiguous electron density that is difficult to interpret. The ligand validation statistics suggest over-interpretation, even for the most active compounds like diflunisal. The primary technical reason is its position on a crystallographic 2-fold axis in the most common crystal form. Further investigations with the use of polyethylene glycol (PEG) to crystallize TTR complexes have resulted in a new trigonal polymorph with two tetramers in the asymmetric unit. The ligand used to obtain this new polymorph, 4-hydroxychalcone, is related to curcumin. Here we evaluate this crystal form to understand the contribution it may bring to the study of TTR ligands complexes, which are often asymmetric. (C) 2016 Elsevier Inc. All rights reserved.