We developed a hands-on course in molecular biology for undergraduate underrepresented in medicine (URM) students. To incentivize student preparation for team-based learning (TBL) activities, we implemented a novel grading schema that requires a minimum individual readiness assurance test (iRAT) score to share the team group readiness assurance test (gRAT) score. Fifty-one students participated in this 2-year study and were divided in teams of five or six students that worked throughout the course on a unique, hands-on project and also participated in TBL exercises. In the laboratory sessions, students isolated RNA from cultured neuronal cells, synthesized complementary DNA (cDNA), and used gene sequencing to identify a gene relevant in human health and disease. Student participation in TBL was quantified and correlated with performance on individual iRATs and the course final examination. We found that implementation of the novel incentive structure lowered the variance of TBL scores (iRAT and gRAT) and strengthened the correlation between final examination scores and either iRAT scores or percentage participation in TBL. Subgroup analysis showed that with the new grading schema, stronger students benefited more from the gRAT exercises, while more poorly performing students were better helped by individual preparation prior to the iRAT exercise. A combination of two active learning strategies, TBL and hands-on sessions, may strengthen student acquisition of course content and promote teamwork skills. The new incentive structure seems to reduce the disparity in knowledge amongst our students as demonstrated by the reduced iRAT and gRAT score variances.