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Abstract Anaplastic lymphoma kinase (ALK) rearrangements are drivers of a subset of non‐small cell lung cancer (NSCLC). The rapid progression of ALK inhibitors has significantly prolonged the progression‐free survival of patients with ALK gene‐sensitive mutations. However, the response of patients with rare ALK rearrangements to tyrosine kinase inhibitors remains unknown. Here, we report a rare case of striatin (STRN)‐ALK‐positive NSCLC showing primary resistance to first‐line therapy alectinib and limited clinical activity of crizotinib in the alectinib‐resistant setting.