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The tyrosine kinase inhibitor crizotinib is an effective therapy for patients with cancers harboring rearrangements of the anaplastic lymphoma kinase (ALK) gene. Here, we describe two patients with advanced ALK-positive lung cancer who developed hypersensitivity to crizotinib, requiring temporary discontinuation of the drug. Both patients were treated with a rapid oral desensitization protocol allowing them to resume crizotinib without further signs or symptoms of hypersensitivity.