Investigations on thermal behavior are essential during the development of therapeutic proteins. Understanding the link between thermal unfolding and aggregation might help to minimize conformational and colloidal instabilities. In this study, a therapeutic monoclonal antibody (MAb) and its Fab and Fc fragments were investigated by differential scanning fluorimetry, temperatureramped dynamic light scattering and turbidity measurement. Repulsive net charges at the low pH increased the colloidal stability, although a reduction of the conformational stability was observed. Aggregation was driven by hydrophobic interactions. Thus, the presented methods described and explained the thermal behavior of the protein and demonstrated their value for the development of pharmaceutical protein products. Coupling of differently charged hydrophobic payloads affected colloidal stability mostly based on the charge effects. The combination of orthogonal methods allows a better understanding of the conformational and colloidal stability of mAbs and mAbconjugates.