The potential contribution of digital tools to quality instruction is a widely debated issue in STEM education. As a first step to investigate this potential, it is necessary to understand how instructional quality and digital tool use are interrelated. Although previous research generally hinted that instructional quality and the use of digital tools are related, it is unclear how these relations are specific to different STEM subjects. Addressing this research gap, we compared the association between instructional quality and the use of digital tools in biology (Study 1) and mathematics lessons (Study 2) based on the questionnaires answered by N = 2,396 eight-grade students at German secondary schools. On the basis of Latent Profile Analyses of instructional quality features considering both their class-level and their within-class variability, the use of digital tools was compared for the profiles of instructional quality identified for biology and mathematics lessons. Study 1 showed, that the three profiles in biology significantly differed in their use of digital tools, whereas this was not the case with the four profiles identified in mathematics (Study 2). In biology, digital tools had been more often implemented in high-quality than in low-quality lessons. But there was no such difference in mathematics. It was conspicuous that students in biology lessons reported overall more digital tool use than in mathematics. Despite several similarities between STEM subjects, the results suggest that a subject-specific perspective on instructional quality and the use of digital tools is beneficial for a more nuanced approach to teacher training.