ObjectiveDespite the promising efficacy and tolerability of alectinib in treating advanced anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), the role of alectinib in neoadjuvant setting remains understudied in ALK-rearranged resectable lung cancer.MethodsOur report concerns two cases of early-stage NSCLC with complete pathologic responses to off-label use of long-course neoadjuvant alectinib. PubMed, Web of Science, and Cochrane Library were searched comprehensively for ALK-positive resectable cases with neoadjuvant alectinib. The papers were chosen following PRISMA recommendations. Seven cases from the literature and two present cases were evaluated.ResultsTwo cases with stage IIB (cT3N0M0) EML4-ALK lung adenocarcinoma received long-course (more than 30 weeks) of neoadjuvant alectinib followed by R0 lobectomy with the complete pathological response. In our systematic review, 74 studies were included in the original search. Application of the screening criteria resulted in 18 articles deemed eligible for full-text reading. Following the application of the exclusion criteria, out of six papers, seven cases were selected for inclusion in the final analysis and were included in the systematic review. None of the studies were included in the quantitative analysis.ConclusionWe report two cases of lung adenocarcinoma with resectable ALK-positive that achieved pCR with long-course neoadjuvant alectinib. Our cases and a systematic review of the literature support the feasibility of neoadjuvant alectinib treatment for NSCLC. However, large clinical trials must be conducted in the future to determine the treatment course and efficacy of the neoadjuvant alectinib modality.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42022376804.