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Chromosomal rearrangements involving the c-ros oncogene 1 ( ROS1 ) gene define a subset of non-small cell lung cancers highly sensitive to small-molecule tyrosine kinase inhibitors. However, little is known about the impact of different fusion partners on tyrosine kinase inhibitor efficacy. We herein describe a case of a 26-year-old never-smoker patient from southern Africa with metastatic lung adenocarcinoma driven by SLC12A2 - ROS1 fusion, who had a pronounced and durable response to crizotinib. The present case underscores the importance of pursuing actionable alterations in patients with similar clinical and epidemiological characteristics. In addition, provides the second report of crizotinib activity against lung malignancies harboring the unique SLC12A2-ROS1 fusion and highlights the importance of a deeper understanding of molecular alterations in underrepresented subgroups of patients to tailor the decision-making in daily practice., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.F.S.A.R. has received support for attending meetings and travel expenses from Foundation Medicine. K.P.S. has received support for attending meetings and travel expenses from Astra-Zeneca. She has also received honoraria from Eurofarma. All other authors have no conflicts of interest to declare., (© The Author(s) 2022.)