Teachers need knowledge about operant conditioning as an important way to prevent student misbehavior. In an experiment with 181 student teachers, we investigated how the acquisition of conceptual knowledge about operant conditioning can be promoted through case comparisons. Our results showed that case comparison effectively supported the acquisition of knowledge about operant conditioning. Knowledge acquisition was higher with more guidance during case comparison by providing key features to be used to compare the cases. Furthermore, with more guidance student teachers learned more efficiently. In addition, higher germane load and lower extraneous load were found to mediate the effect of instructional guidance on learning. The case comparison was also associated with a shift in student teachers' beliefs, with more appropriate beliefs about operant conditioning afterwards. Thus, the results indicate that case comparison is an effective approach to promoting the acquisition of conceptual knowledge and positive beliefs about operant conditioning.