A limitation of LUAD patient-derived xenograft (PDX) LUAD models is that they do not develop metastases. To address this limitation, while still preserving the use of patient-derived cancer tissue, we developed a LUAD patient-derived organoid (PDO) platform. All PDOs are clinically and genomically (MSK-IMPACT, 468 genes) annotated. Preservation of histologic architecture and concordant genomic profiles between the primary tumor and corresponding PDO were confirmed by our pathologist and MSK-IMPACT, respectively. To explore if LUAD PDOs possess metastatic potential, we developed 2 PDO metastatic models for different applications: 1) a subcapsular splenic implantation metastatic model, where large primary tumors formed in the spleen with microscopic metastases developing weeks later in the lung and liver; and 2) an intracardiac injection metastatic model, which reveals the metastatic capabilities of PDOs to different organs. Utilizing our PDO platform, we are particularly interested in exploring how the genetic alterations and the pertubation of chromatin landscape contribute to tumorigenesis and metastases of LUAD with specific histopathologies.