In this report, immediate alectinib administration for ALK-altered Lung-CUPs helped the patients’ survival....Epidermal growth factor receptor (EGFR) mutation was negative. ALK overexpression was observed by IHC and rapid fluorescence in situ hybridization (Fig. 2e, f). Consequently, alectinib (600 mg/day) was administrated on February 8, 2018 (Fig. 1). On February 23, 2018, CT indicated a partial response (PR) in all targets, and on April 9, 2018, complete response (CR) was achieved (Fig. 1, 1, 2g). CR has been maintained for 3 years and 4 months until now (Fig. 1, 1, 2h) with no severe adverse events.