Thyroid Peroxidase (TPO) is a membrane-bound dimeric protein essential for the biosynthesis of thyroid hormones, and is a major autoantigen of autoimmune thyroid diseases. Understanding the structural basis for TPO’s autoimmunity will provide key insights into the breakdown of immune tolerance in thyroid autoimmune disease.  TPO has been a major target for structural studies for over 20 years. However, to date, no structure of TPO has been determined. In order to address this, we used a molecular modelling approach to investigate plausible modes of TPO dimer organisation.   TPO has a high level of homology to other animal peroxidases in its catalytic domain (termed the MPO domain). However, TPO also has additional domains, including a putative transmembrane (TM) anchor, a complement control protein (CCP) domain and an epidermal growth factor (EGF) domain. We produced several models of TPO. Consideration of the biological role of TPO allowed us to select plausible arrangements of the MPO, CCP, EGF and TM domains. Numerous studies have identified regions on TPO important for autoantibody binding. By mapping these epitopes onto our model, we provide a platform for understanding the antigenicity of TPO. Our model provides a useful tool for investigating autoimmunity, as well as tackling the challenge of producing crystals suitable for X-ray crystallographic investigation of the structure of TPO.