Although the field of epistemic cognition is still growing, only few studies so far have dealt with the question of how epistemic beliefs of school children can be described in a valid way, taking different learning opportunities as possibilities for developmental trajectories into account. A valuable research approach to overcome some of the methodological problems might be classifying students into homogeneous groups according to their epistemic beliefs in science. In our study, we ask 1) what kind of science-related epistemic profiles, exist across grades 5 to 12, 2) how these profiles differ with regard to learning related outcomes, and 3) how students’ epistemic belief profiles change during secondary school? A longitudinal survey with two starting cohorts (grades 5 and 9) was administered to secondary school students over a period of 4 years. The results indicate that it is valuable to identify distinctive groups of students with homogenous science-related epistemic belief patterns in both cohorts. Furthermore, results show that the epistemic belief patterns differ with regard to motivational and cognitive outcomes indicating more helpful but also more diametrical patterns of beliefs with respect to science learning in school. Moreover, results of transition analyses strengthen the finding of high stability of students’ beliefs. The results will be discussed with regard to learning opportunities in every-day school live as well as adaptive interventions for specific subgroups of students for a helpful development of students’ beliefs about knowledge and knowing for science learning.