A 55-year-old Asian never-smoker female presenting with an irritable dry cough for a month was examined in a community hospital in October 2013. Computed tomography (CT) scan of chest revealed a single pulmonary nodule (approximately 2.5 × 5 cm) on the lower left lobe and enlarged subcarinal lymph nodes. No metastases in brain, liver, bone and so on were found. After biopsy of the left lung lesion, she was diagnosed as lung moderately differentiated adenocarcinoma and the stage was IIIA (cT2N2M0). She was recommended for two cycles of inducing chemotherapy with docetaxel (75 mg/m2 D1 − D1 = D21) and cisplatin (75 mg/m2 D1 − D1 = D21) and then the concurrent radiotherapy and chemotherapy. However, the primary lesion on the lower left lobe was larger and new metastasis in the right upper lobe was found after these two cycle chemotherapy. Re-evaluation and genotype testing of the left lung lesion showed no EGFR mutation, but luckily, the strong expression of ALK (ventana); and EML4-ALK gene fusion was positive by fluorescence in situ hybridization. The patient received crizotinib treatment (250 mg, bid, orally) starting from 7 Jan. 2014. The primary lesion on the lower left lobe and metastasis in the right upper lobe was disappeared 1 month later. Stable condition maintained until 30 Jun. 2014 when metastatic nodules were found on liver. Microwave ablation was used to treat with these metastatic nodules. And crizotinib was continued until 20 Aug. 2014, when liver lesions enlarged again. Then the patient began to receive ceritinib (750 mg, qd, orally) from 8 Oct. 2014; 1 month later, the liver metastasis shrinked apparently (partial response, PR). However, adverse events including acute liver function lesion (CTCAE) (grade 2/CTCAE ver. 4.0) and severe diarrhea occurred. The ceritinib dose was then decreased from 750 to 450 mg. Although there were no other metastases, the treatment was discontinued because of liver metastasis progression in March 2015. The patient came to our hospital on 4 May 2015. After the re-biopsy of liver metastasis, three EML4–ALK resistance mutations (C1156Y, D1203N and L1198F) was found. The patient began to receive treatment of pemetrexed (500 mg/m2 D1 − D1 = D21) with bevacizumab (5 mg/m2 D1 − D1 = D21) from 11 May 2015. After two cycle treatment, metastatic nodule size in liver decreased, and there were no new metastases in bilateral lungs, brain and so on, which demonstrated the disease of PR. After four and six cycle treatment, the CT scan both revealed stable disease. The patient tolerated well and the performance status is 1. Following additional two cycle of pemetrexed with bevacizumab, the liver metastatic tumor showed radiographic progression by the CT scan on 4 Dec. 2015. The best supportive care was administrated, and the patient ultimately died of liver failure in March 2016.