Non Small Cell Lung Cancer (NSCLC) is one of the most significant causes of cancer-related mortality worldwide. In about 6-7% of NSCLC, rearrangements involving the Anaplastic Lymphoma Kinase (ALK) play a strong driver role in tumor progression. Indeed, blocking ALKs kinase activity with the use of selective kinase inhibitors, such as crizotinib, induces an exceptionally high rate of clinical responses in ALK-rearranged NSCLC. Unfortunately, almost all patients relapse due to resistance to crizotinib developed in tumors by various molecular mechanisms. Therefore, developing additional therapeutic options for ALK-rearranged NSCLC is a pressing clinical need. The ALK protein has many, quite unique, features of an ideal tumor onco-antigen: it is specifically expressed by tumor cells with very low and limited expression in normal tissues, it is naturally immunogenic in humans, as indicated by studies on patients with ALK-rearranged tumors, and it is required for tumor survival and growth, which greatly decreases the chances of ALK negative clones to escape the immune system. In preclinical experiments in mouse models of ALK-driven cancers, we demonstrated that DNA-based ALK vaccine elicited a specific and powerful immune response against the ALK protein that was sufficient to strongly reduce the growth of ALK-rearranged lymphoma and lung carcinoma. Based on this data, we predict that a highly potent and safe ALK-targeted vaccine will be beneficial for the treatment of lung cancer and lymphoma patients. In principle, this vaccine could be extended to any ALK-expressing cancer.