Students' argumentation skills are considered a central tool to contribute to scientific controversies in the science classroom. Scientific controversies of social relevance (socioscientific issues; SSI) are subject to multiple viewpoints that are often rooted in diverse disciplines. However, the relationship between issue familiarity and students' multidisciplinary argumentation is still a matter under discussion. This study: (1) explores whether the selection of a particular issue (animal testing) enables students' engagement in multidisciplinary argumentation without additional issue familiarisation, i.e., using only their existing knowledge; and (2) clarifies the relationship between increased issue familiarity and students' multidisciplinary argumentation. One hundred and sixty three ninth and tenth graders participated in this study, of whom one hundred and six took part in a teaching unit to familiarise themselves with the issue of animal testing. The study's results demonstrate that animal testing constitutes an effective issue to engage students with the complexity of SSI without requiring more than basic familiarity prior to engagement. The results further demonstrate that increased issue familiarity can enhance the overall diversity of discipline-related arguments amongst students; however, not all disciplines were enhanced equally. The findings suggest that more instructional guidance seems to be needed to assist students in broadening their arguments.