Background: Microorganisms are very important in day-to-day life, but they are inadequately addressed in the Spanish educational system. It is essential that students are well informed about their characteristics and functions. Purpose: The study aims to find out primary school students' perceptions of microorganisms and to analyze whether theoretical or practical teaching interventions produce different levels in student's learning about this topic. Sample: The sample consisted of 199 primary students in 2nd (aged 7-8) and 6th (11-12) grades from two public schools in Albacete (Spain). Design and method: This study uses a pre- and post-intervention questionnaire to evaluate the knowledge of students on the issue of microorganisms. We compare differences by age and two teaching-learning intervention methodologies: theoretical and practical. Results: Results from the pre-test showed a poor understanding and several misconceptions. Children have a limited and negative view of microorganisms, mainly derived from non-formal learning. Both types of intervention provided an improvement in knowledge, but closed questions did not reveal clear statistically significant differences between methods. Open questions showed how the scientific use of the language and quality of verbalization is much better in the groups that received a practical intervention. Conclusion: The findings can be a starting point for curriculum planners and for teachers interested in engaging students in science learning.