This structured set of lab activities allows students to explore the evolution of pelvic spine reduction in stickleback fish. The exercise draws upon the field of evolutionary and developmental biology (evo-devo) and information presented in the HHMI Holiday Lecture entitled “Fossils, Genes, and Embryos.” Students analyze fossil data from a rich stickleback deposit in Nevada, documenting the evolution of pelvic spine reduction in a preserved population, and then use Hardy-Weinberg analysis to explore the role of natural selection in this type of evolutionary event. Finally, students use molecular genetics and polymerase chain reaction to uncover the evolutionary role of gene switches in pelvic spine reduction. Collectively, the lab activities explore a specific evolutionary event from the combined perspectives of fossil evidence, natural selection, and molecular genetics. The lab also serves as a good introduction to the concepts of gene switches and evo-devo.