Histologic examination of biopsy and enucleation specimens in patients with uveal melanoma can confirm the diagnosis when clinical investigation is inconclusive. Histologic predictors of metastasis enhance prognostication, especially with multivariable analysis including anatomic and genetic predictors. After enucleation, microscopic assessment of extraocular spread may help identify patients who require adjunctive external beam radiotherapy. Histologic investigation also provides insights into the pathophysiology of uveal melanomas as well as the morbidity that can be caused by the treatment of this disease. This chapter highlights the most significant histopathologic features of uveal melanoma.