Teaching large classes is increasingly common; thus, demand for effective large-class pedagogy is rising. One method, titled "SCALE-UP" (Student-Centered Active Learning Environment for Undergraduate Programs), is intended for large classes and involves collaborative, active learning in a technology-rich and student-centered environment. The authors focus on one undergraduate SCALE-UP Cancer Biology course at a large public university. They investigated the course following an instrumental case study design in which they examined students' motivation and engagement. Data suggest that motivation-related perceptions were highly positive, and they offer an analysis of the influential instructional practices and course structures.