Differentiated instruction is considered to be an important teaching quality domain to address the needs of individual students in daily classroom practices. However, little is known about whether differentiated instruction is empirically distinguishable from other teaching quality domains in different national contexts. Additionally, little is known about how the complex skill of differentiated instruction compares with other teaching quality domains across national contexts. To gain empirical insight in differentiated instruction and other related teaching quality domains, cross-cultural comparisons provide valuable insights. In this study, teacher classroom practices of two high-performing educational systems, The Netherlands and South Korea, were observed focusing on differentiated instruction and other related teaching quality domains using an existing observation instrument. Variable-centred and person-centred approaches were applied to analyze the data. The study provides evidence that differentiated instruction can be viewed as a distinct domain of teaching quality in both national contexts, while at the same time being related to other teaching domains. In both countries, differentiated instruction was the most difficult domain of teaching quality. However, differential relationships between teaching quality domains were visible across teacher profiles and across countries.