Lung cancer is the leading cause of cancer-related death. NSCLC accounts for 80-90% of cases. In younger patients, adenocarcinoma is the most frequent histotype and 3-7% expresses the rearrange-ment of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by FDA. We present the case of a 17-year-old male with metastatic naïve ALK-positive adenocarcinoma, treated with crizotinib. He received crizotinib and obtained a prolonged response with PFS of 33 months. Crizotinib can be extremely effective in adolescent with naïve ALK-positive NSCLC but it hardly penetrates blood-brain barrier. Resistance mechanisms will be investigated for a better man-agement.