International research associates transformational leadership applied by the school leader with the effective teaching of the teacher. Differentiated teaching is considered a holistic way of approaching the learning process and a vital component of effective teaching. The purpose of the present study is to investigate whether Greek teachers differentiate their teaching according to their students' interests and needs and whether transformational leadership influences this implementation. The sample of the research consisted of 147 secondary education teachers in the region of Eastern Macedonia and Thrace. The results revealed that the 73.5% of teachers apply differentiated teaching. There was also a statistically significant but weak positive correlation between the three sub-factors of transformational leadership, charisma, individualized consideration, and intellectual stimulation, with differentiated teaching. Principal’s charisma has the highest positive correlation than the other two sub-factors and can predict the application of differentiated teaching at 9.3%. The findings of the research could be used to train potential principals in transformational leadership practices.