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OBJECTIVE We aim to describe two cases of creatine phosphokinase (CPK) and liver enzymes elevation occurring as adverse effects of alectinib (Alecensa) treatment for anaplastic lymphoma kinase (ALK)-mutated metastatic nonsmall cell lung cancer (NSCLC). METHOD A 56-year-old female and a 59-year-old male diagnosed with NSCLC exhibiting ALK gene rearrangements were treated by alectinib administration. RESULTS The former had a complete response of widespread metastatic disease within 3 months, and the latter also had a substantial response. Both patients initially experienced an episode of CPK elevation and neither had dose modifications. At the end of the treatment, CPK and liver enzymes returned to normal range despite the continuation of alectinib full dose. CONCLUSION A transient elevation of CPK and liver enzymes may take place during the alectinib treatment, indicating a tumor tissue damage thus contributing to a significant response.