UM orthotopic xenografts generated from PDOs resemble the corresponding clinical tumor. Patients with a unilateral, large, pigmented choroidal mass (black outline) consistent with primary UM donated tumor tissue for LAD28 (BAP1 retained) and LAD39 (BAP1 loss). H&E-stained slides are shown of the primary clinical tumor (100×). BAP1 immunohistochemistry of the primary tumors of origin for LAD28 and LAD39 revealed retention or loss of nuclear BAP1 expression, respectively (200×). PDOs were generated from a FNAB of each clinical sample, and light microscopy (100×) and H&E (400×) images of LAD28 and LAD39 are shown. BAP1 immunohistochemistry of PDOs (400×) showed recapitulation of BAP1 retention or loss, matching the primary tumor. Murine orthotopic xenografts were generated from LAD28 (n = 2) and LAD39 (n = 2) via suprachoroidal injection of approximately 150,000 cells. The injected eye developed pigmented choroidal masses (black outline), simulating in vivo human pathology. H&E and nuclear BAP1 immunohistochemistry of the tumors from enucleated mouse eyes matched the primary human tumor.