Uveal melanoma (UM) has a propensity for metastasis which results in high mortality.1,2 As metastases are rarely detectable at the time of diagnosis, great efforts have been directed toward accurate prognostication and identifying high-risk factors for metastasis.3-5 One can differentiate between clinical, histopathologic, and genetic prognostic factors.6 However, this chapter reveals the breadth of parameters that must be taken into account when trying to predict a patient’s prognosis.7 These include, but are not limited to, the age of the patient, tumor-specific factors, patient comorbidities, the effectiveness of local treatment, and a plethora of tumor-associated mutations and aberrations, all of which influence the risk for metastatic disease.6,8,9