Small molecule-induced selective degradation of target proteins is one of the most promising new generation drug discovery approaches. Small bifunctional molecules like PROTACs can induce the recruitment of a target protein to an E3 ligase, forming a ternary complex to facilitate the target’s degradation via the cellular proteasome. This application note introduces a mass photometry-based assay, which can inform on the key aspects of the ternary complex formation. Mass photometry experiments do not require protein labelling or immobilisation and therefore allow direct visualisation and quantification of true molecule behaviour in solution.