The main objective of the present study was to evaluate the effectiveness of two learning methodologies in a Plant Tissue Culture course of a Biotechnology degree--lecture-based and hybrid project-based learning--in which a project assignment was included. The effectiveness of these two systems was compared based on the students' knowledge acquisition and the perception of their satisfaction. In this study, we evaluated the scores obtained by students in a written exam and the results of a satisfaction survey. The assessment showed that students attained improved marks in the written exam after being taught using the hybrid method. The incorporation of the project assignment in the Plant Tissue Culture program also improved the general perception that the students had of the course. The project assignment allowed the students to achieve new learning outcomes directly related to experimental work and the scientific method. The teachers perceived the hybrid project-based learning method positively, as students not only improved their knowledge gain, but were also more involved in the course.