Non-small cell lung cancer comprises different types of molecular subsets: adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and non-otherwise specified. The most common mutation occurs in the epidermal growth factor receptor, particularly in exon 21 and exon 19 deletions. These mutations confer constitutive activation of the epidermal growth factor receptor tyrosine kinase domain. The frequency of epidermal growth factor receptor mutations varies among different ethnic groups. The anaplastic lymphoma kinase gene gained strong clinical interest when it was found to be translocated in anaplastic large cell lymphoma, and subsequently in diffuse large B-cell lymphoma, inflammatory myofibroblastic tumors, and non-small cell lung cancer. Activating anaplastic lymphoma kinase translocations dictate favorable and often dramatic responses to anaplastic lymphoma kinase tyrosine kinase inhibitors like crizotinib. Thus, the recognition of this molecular alteration is quite important in clinical practice. Therefore, the main objective of this manuscript is to confirm the relevance of the anaplastic lymphoma kinase tyrosine kinase inhibitors to treat non-small cell lung cancer. Hence, we report a case of advanced non-small cell lung cancer harboring anaplastic lymphoma kinase translocation treated at the Instituto Nacional de Cancerología in Mexico. We conclude that many questions remain unanswered: whether to use first- or second-generation anaplastic lymphoma kinase inhibitors, treatment time, sequencing, order, and the selection of an anaplastic lymphoma kinase inhibitor in clinically specific situations like brain metastasis. We need further investigations to address these problems.