The generation of reliable and certain evidence is among the central objectives of the natural sciences. However, in real-world scientific research, dealing with uncertainty is often a necessary part of the establishment of certain knowledge. Therefore, science teaching has to take into consideration the fact that evidence is not only reliable: Whenever science is still in the making, evidence may be temporarily uncertain, varying, and fragile. This study reconstructs aspects of science teachers’ professional competence as well as their orientational frameworks when dealing with uncertain evidence in science teaching. Semi-structured interviews with video vignettes used as interview stimuli were conducted with 26 science teachers. The video vignettes were carefully designed and validated in order to illustrate situations in which uncertain evidence unexpectedly arises during science teaching. The generated data were analyzed based on the documentary method and qualitative data analysis. Results indicate that teachers employ a variety of strategies for dealing with uncertain evidence. Furthermore, our results point to connections between teachers’ instructional strategies and their beliefs about their own and their students’ roles.