Recently, the field of biology has recognized the importance of early introduction to authentic research experiences in the classroom (i.e. Course-based Undergraduate Research Experiences; CUREs). While studies focused on introductory-level courses demonstrate the benefits of this teaching methodology on student outcomes, their efficacy in upper-level courses is understudied. Upper-level courses typically possess unique elements when compared to introductory courses including (1) class size, (2) course complexity, (3) student confidence levels, (4) professional applicability of learned skills, and (5) the potential for independence. For instructors, one of the most challenging aspects of upper-level CUREs is balancing structure and independence to maximize student outcomes. Here, we compare self-reported student outcomes from two sections of an upper-level biology CURE over a period of two years. While both sections focused on molecular biology research, one section was provided a structured skill-building section preceding their independent research, while the other was offered immediate independence in developing those skills. Student survey reports of confidence, professional applicability, and CURE structure indicate that the inclusion of skill-building led to more positive impacts than when students had increased independence. We discuss our results in the context of each unique element of upper-level courses, focusing on how a blend of skill-building and independence may affect student outcomes. This work is especially relevant for those who teach upper-level CUREs or train and employ undergraduates to conduct research.