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This study explored the opinions of teachers and 14-16 year old students about the teaching of the origin of life in Science and RE. It focused on any discontinuities between students’ religious or cultural backgrounds and what they are taught in school. A mixed methodology was used: a national teacher survey and work in four case schools (teacher interviews, student questionnaires, student focus groups). The case schools represented three contexts: a Christian faith school, a non-faith school with predominantly Muslim catchment, and two non-faith, mixed catchment schools. Grounded theory guided the design and analysis. Most Science teachers mentioned religious beliefs in their teaching of the origin of life, and most RE teachers mentioned scientific theories. However, there was little cross-departmental collaboration, raising the concern of inaccurate teaching of science theories in RE and potentially insensitive, counter-productive treatment of religious students in Science. Students tended to perceive Science as based on fact and closed to questioning or discussion of their concerns whereas RE had a more interactive pedagogy, encouraging challenge and the expression of opinion. Two complementary frameworks were developed from the data. One is a taxonomy of the different ways science and religion are seen to inter-relate. The other, which has been set in the context of the cross-cultural border crossing literature, reflects the propensity to engage with the science/religion interface as exemplified by the topic of the origin of life. Many Muslim students resisted engagement because of conflicting religious beliefs. Teachers did not always appreciate the extent to which this topic troubled some students who needed help to accommodate clashes between science and their religious beliefs. Building up cross-curricular working may increase teacher knowledge and confidence as well as providing better support for students. The engagement typology could be used to develop a simple questionnaire to enable teachers to assess student responsiveness before tackling potentially sensitive or controversial topics.