Visual representations play a critical role in the communication of science concepts for scientists and students alike. However, recent research suggests that novice students experience difficulty extracting relevant information from representations. This study examined students' interpretations of visual representations of DNA replication. Each of the four steps of DNA replication included in the instructional presentation was represented as a text slide, a simple 2D graphic, and a rich 3D graphic. Participants were middle grade girls (n = 21) attending a summer math and science program. Students' eye movements were measured as they viewed the representations. Participants were interviewed following instruction to assess their perceived salient features. Eye tracking fixation counts indicated that the same features (look zones) in the corresponding 2D and 3D graphics had different salience. The interviews revealed that students used different characteristics such as color, shape, and complexity to make sense of the graphics. The results of this study have implications for the design of instructional representations. Since many students have difficulty distinguishing between relevant and irrelevant information, cueing and directing student attention through the instructional representation could allow cognitive resources to be directed to the most relevant material.