Literature affirms that teachers' difficulties in mastering the subject content and its teaching can be responsible for students' negative attitudes towards that subject. The present study sought to explore biology topics in the revised Rwandan curriculum which teachers have difficulties in teaching, the reasons for their difficulties, and ways to improve teaching and learning of such topics. Data were collected from a sample of 67 teachers who agreed to join the survey, and analysed both quantitatively and qualitatively. The results showed that 17 topics were considered difficult to teach and to learn. Molecular biology and biotechnology-related topics such as genetic engineering, gene technology, genetics, cell division, DNA replication, and protein synthesis were perceived as the most difficult to teach and learn. Teachers indicated a lack of content knowledge and visual teaching materials, inability to organise practical activities, overloaded curriculum, and the topics' abstractness to be among the reasons for the difficulty. Teachers suggested the use of virtual labs, 3D animations, provision of laboratory materials, reduction of the curriculum content, training and study visits as the practical options to alleviate the difficulties. Furthermore, the authors recommended different teachers' professional development approaches and areas of focus for future research