Implementing biotechnology education through hands-on teaching methods should be considered by secondary biology teachers. This study is an experimental research design to examine increased student content knowledge in biotechnology after a hands-on biotechnology intervention. The teachers from both school groups participated in, Project Crawfish, a biotechnology professional development program. Students from both schools completed a pre and post assessment. The classroom was the unit of analysis. When the assessment was analyzed, each school had statistically significant increases in student content knowledge (p less than 0.0001 for the intervention school and p = 0.0481 for the control school). When the schools were compared to each other, a p-value of 0.0543 provided a suggestive relationship that the biotechnology intervention school had a larger increase in student content knowledge overall. When the assessment was divided into the five components, the intervention school showed significant increases in all five components. The control school had significant increases in student content knowledge in the PCR and DNA sequencing components (p = 0.0459, p = 0.0043, respectively).