The language in science classrooms has specific characteristics related to the use of words, grammar, and semantic patterns that may be a particularly challenging issue for students meaning making of science phenomena. The aim of the presented project is to investigate language related issues in relation to meaning making of school science in multilingual settings. This is done through a multidisciplinary (science education and linguistics) and quantitative approach in Swedish secondary schools. The research question is “what kind of words are challenging for students with Swedish language background and students with other language backgrounds”. Meaning making of words was estimated through web-based vocabulary tests given to 232 students in grade 7-9. In addition, the students were asked about their first language and how long time they studied in Swedish school. This data made it possible to calculate potential significant differences between groups of students and categories of words. On a general level, significant differences were found between the performance of students with Swedish as mother tongue and those with other mother tongues and within the group that arrived in Sweden later than school start. When focusing word types, we found differences between the groups in relation to two categories: “general academic words” (e.g. cause and consist of) and “colloquial but content related words” (e.g. pass and branch). On the other hand, difficult word categories for all students were “academic and content-related words” (e.g. trait and process) and “academic and content-typical words” (e.g. occur and indicator). We argue that, especially regarding students with another mother tongue than the language of instruction, it is important to give attention to the words that are general academic words along with the common focus on content-specific words – the concepts.