Visualizing anatomical structures and functional processes in three dimensions (3D) are important skills for medical students. However, contemplating 3D structures mentally and interpreting biomedical images can be challenging. This study examines the impact of a new pedagogical approach to teaching neuroanatomy, specifically how building a 3D-model from oil-based modeling clay affects learners' understanding of periventricular structures of the brain among undergraduate medical students in Colombia. Students were provided with an instructional video before building the models of the structures, and thereafter took a computer-based quiz. They then brought their clay models to class where they answered questions about the structures via interactive response cards. Their knowledge of periventricular structures was assessed with a paper-based quiz. Afterward, a focus group was conducted and a survey was distributed to understand students' perceptions of the activity, as well as the impact of the intervention on their understanding of anatomical structures in 3D. Quiz scores of students that constructed the models were significantly higher than those taught the material in a more traditional manner (P < 0.05). Moreover, the modeling activity reduced time spent studying the topic and increased understanding of spatial relationships between structures in the brain. The results demonstrated a significant difference between genders in their self-perception of their ability to contemplate and rotate structures mentally (P < 0.05). The study demonstrated that the construction of 3D clay models in combination with autonomous learning activities was a valuable and efficient learning tool in the anatomy course, and that additional models could be designed to promote deeper learning of other neuroanatomy topics.