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About 50% of patients with choroidal melanoma develop metastatic disease, despite successful eradication of the primary tumor. Patient care is complicated by the fact that we do not know whether ocular treatment ever influences survival and if so in whom. Some authorities believe that metastatic spread is never preventable, because it has always occurred by the time the ocular tumor is detected. Others hold the view that metastatic spread can occur late, at least in some patients, in whom timely and successful treatment is life-saving. Some melanomas never seem to metastasize, even if they reach an advanced stage. It is likely that many patients are undergoing futile enucleation or experiencing severe ocular morbidity and visual loss from excessive radiation safety margins in the hope of living longer. Some of these patients would do better with tumor resection, often rejected because of concerns about iatrogenic tumor dissemination. At the same time, many patients with a small melanoma are being left untreated for years until growth is documented, possibly missing opportunities for prolonging life. Metastatic disease is highly likely when genetic tumor analysis detects monosomy 3, chromosome 8q gain, a class 2 gene expression profile, and/or BAP1 loss. Do these lethal genetic aberrations ever develop while the patient is under observation? If so, can these be predicted by genetic analysis? Do lethal mutations and metastasis ever occur because ocular treatment has failed to eradicate the tumor completely? Answers to these questions would profoundly change the management of patients with uveal melanoma.Does ocular treatment for choroidal melanoma prevent metastasis?Do all choroidal melanomas with lethal mutations metastasize?Does treatment delay allow melanomas to develop lethal mutations and metastasize?Does radiotherapy failure allow or cause lethal mutations and metastatic death?Can BAP1 deletion be a surrogate for metastasis when studying therapeutic efficacy?