Most molecular biology and biological sciences students understand that the polymerase chain reaction (PCR) is used to amplify DNA. However, we have found that some students experience conceptual misunderstandings, a lack of detailed comprehension of the PCR process, or difficulties with troubleshooting and predicting the effects of alterations to the standard PCR process. We hypothesized that a problem-based learning approach that incorporates a kinesthetic modeling of the PCR process could address these problems. During this hands-on learning activity, students “amplified” a specific region of template DNA through three cycles of PCR using a “toolkit” composed of a) intertwined, supercoiled, and double-stranded yarn representing template DNA, b) short wax sticks representing primers, and c) long wax sticks representing the PCR products. Instructors can introduce a variety of assessments, including real-time image capture of the models, pre- and post-activity assessment quizzes, and homework assignment to gauge student learning. We administered identical four-question quizzes worth 12 points to 28 undergraduate students before and after the activity. The mean score on the post-quiz was three points higher than the pre-quiz score, demonstrating a 75% increase in score. Moreover, we found that students who began the activity with lower levels of understanding experienced the most significant learning gains. This hands-on, student-centered, kinesthetic activity allowed students to (i) visualize PCR processes, (ii) construct a model of the PCR process, (iii) correct common misconceptions and sources of confusion, and (iv) actively engage in the learning process.