Anaplastic lymphoma kinase (ALK) rearrangement defines a unique nonsmall cell lung cancer (NSCLC) molecular subtype, of which the patients could potentially benefit from anti-ALKtherapies. So far, the outcomes of the canonical echinoderm microtubule-associated protein-like (EML-ALK) patients subjected to ALKinhibitors are well established. However, given the increasing complexity of ALKfusion partners, as detected by high-throughput sequencing, the responses of those with rare ALKfusion events remain to be explored. Here, we report a lung adenocarcinoma patient with brain metastasis harboring an ARHGAP5downstream intergenic region ALKfusion, as detected by using DNA-based next-generation sequencing, who experienced a partial response to alectinib treatment. While whole- transcriptome RNA sequencing (RNA-seq) failed to identify potential ALK fusion transcripts, subsequent targeted deep RNA-seq revealed the expression of EML4-ALKtranscripts in the tumor tissue. Given the increasing application of the ALK-tyrosine kinase inhibitors (TKIs), it is extremely crucial to define the patients who could be suitable for this treatment in clinic. The present case has provided supporting evidence that noncanonical ALKrearrangements on the genomic level are often functionally relevant and targetable by ALK-TKI, particularly in cases with sub-optimal quantity and quality for RNA validation.