This paper presents a checklist that scaffolds teachers' professional decision-making with regard to differentiated instruction. It discusses the way the concept of differentiated instruction may be applied in an evidence-informed way by presenting a checklist for high-quality differentiated instruction (DI). We tried to tackle the question of how to implement differentiated instruction in a research-informed way. We sought answers in meta-analyses on effective teaching practices. To investigate accordance between this literature and two models for DI, all elements in these models were operationalized. We scrutinized whether the operational elements in these models are characterized by effectivity as effective teaching practices. The result is an evidence-informed checklist that helps teachers who want to apply the concept of DI in their practice which consists of three sets of criteria: (1) the teachers in relation to the students; (2) the teacher and the learning goals; (3) the teacher and the lesson design. The checklist clearly indicates that DI requires a repertoire of teaching methods. Most elements mentioned in both models for DI are supported by evidence-based research, however the application of flexible grouping and the use of learning styles for DI are discussed. This checklist may aid teachers to assess and improve their own teaching practice.