Encouraging students to engage in self-driven problem solving early in their educational career is necessary for them to be able to conduct hypothesis-driven research in the future. However, a fundamental obstacle is finding a topic and activity that is both tangible for students to understand and intelligible. Here we present a classroom activity that can be used in middle school, high school, and even undergraduate college settings to engage students in developing their hypotheses surrounding the human skin microbiome. The ability to culture skin bacteria on agar plates and extract potential environmental factors from their own everyday lives make the human skin microbiome a model example for students to develop their own hypotheses about the variability both within and between different bacterial populations. The approaches we use in our activity set the foundations for how instructors can engage their students in hypothesis-drive scientific research.