The purpose of this study was to examine experienced chemistry teachers' pedagogical content knowledge (PCK) for two different topics in chemistry to better understand how PCK is specific to topic, including whether all components of PCK are topic-specific and to what degree. To explore the topic-specific nature of PCK, we examined two experienced teachers' PCK using a case study methodology. Multiple data collection strategies were used, including a card-sorting activity, Content Representation (CoRe), semi-structured interviews, observations, and field notes. The data collected were analyzed both deductively and inductively. Results revealed that the teachers used more content-based and teacher-centered instruction to teach electrochemistry, whereas their instruction was less teacher-centered, and included Science–Technology–Society–Environment discussions and implicit NOS instruction to teach nuclear reactions. The teachers also varied in the extent of their knowledge of learners and curriculum in comparing their PCK for each topic. In regard to assessment, the teachers' assessment practices were at the general PK level; they lacked topic-specific PCK for either topic. We provided recommendations for professional development programs, pre-service teacher education programs, and curriculum developers to support teachers in developing topic-specific PCK.