Alternatives to fine-needle aspiration biopsy include vitreous-cutter aspiration biopsy, incisional biopsy, excisional biopsy, and liquid biopsy. Vitreous-cutter aspiration biopsy is performed with a 25- or 27-gauge vitreous cutter using a 3-port, sutureless vitrectomy kit, without vitrectomy, retinopexy, or tamponade. Incisional biopsy of choroidal or ciliary body melanomas can be performed with Essen forceps through a deep sclerotomy under a superficial lamellar scleral flap, using tissue glue to close the flap and seal the wound, thereby preventing seeding of tumor cells into surrounding tissues. With excisional biopsy, the entire tumor is removed. Liquid biopsy involves the sampling of aqueous fluid, vitreous, or blood. A biopsy can be performed to establish a diagnosis (e.g., to differentiate melanoma from nevus or metastasis), or to identify the likely source of metastasis when the primary tumor is unknown, or to estimate the survival probability of a patient with uveal melanoma by performing genetic tumor typing and histology. Close collaboration with the laboratory is essential.