Scintigraphy with radiolabeled benzamides was used in melanoma patients. Studies with a newer benzamide called 123I-epidepride, a high-affinity D2 receptor (D2R) antagonist, showed high sensitivity in D2R-positive pituitary adenomas. We evaluated the presence of D2R in patients with uveal melanomas in vivo with 123I-epidepride, and in vitro in melanomas, using immunohistochemistry (IHC) and 125I-epidepride autoradiography. We studied the in vivo tumor-to-background (TB) ratios in six patients with posterior uveal melanoma (one previously enucleated). IHC was performed in 3 of 6 tumors after enucleation and in another 20 uveal melanomas, 7 metastatic lymph nodes from skin melanoma, and 2 normal specimens. 125I-epidepride autoradiography was performed in 10 uveal melanomas (3 of which were studied in vivo), 7 metastases, and 2 normal samples. Radioligand uptake was present in the affected eye of 5 patients with uveal melanoma (TB = 3.1-6.1) and absent in the operated one (TB = 1). Eight uveal tumors were positive at IHC (35%), 14 weakly positive (61%), and 1 negative (4%). Two metastases were positive (29%), 2 weakly positive (29%), and 3 negative (42%). Two uveal tumors were positive at autoradiography (20%), 7 had nonspecific binding (70%), and 1 was negative (10%). One metastasis was positive (14%), while 6 were negative (86%). 123I-epidepride scintigraphy in uveal melanomas seems promising for sensitivity and image quality. D2R was demonstrated in a significant proportion of the melanomas, although 123I-epidepride uptake might also be nonspecific and unrelated to D2R binding. Although further studies on larger series are needed, 123I-epidepride could represent a future tool to study the expression of D2R in other classes of neuroendocrine tumors.