This study evaluated the expression profile of hepatocyte growth factor (HGF), c-Met, epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), and vitreal and serum EGF, HGF, IGF-1 levels in patients with uveal melanoma and assessed their correlation with the clinicopathological parameters. Forty patients with uveal melanoma were included in the study. Clinicopathological parameters were evaluated with hematoxylin-eosin staining. HGF, c-Met, EGFR, and IGF-1R expressions were evaluated immunohistochemically. HGF, EGF, and IGF-1 levels were measured with enzyme-linked immunosorbent assay in vitreous and serum specimens taken at enucleation and 6 months after the enucleation. HGF, c-Met, IGF-1R, and EGFR expressions were detected in 57.5, 20, 20, and 12.5% of cases, respectively. IGF-1R expression was significantly correlated with the degree of pigmentation, necrosis, and lymphocyte infiltration (P = 0.013, 0.04, and 0.017). EGFR expression was significantly correlated with the mitosis rate (P = 0.02). Vitreal EGF and serum IGF-1 levels were significantly higher in patients with scleral invasion (15.72 +/- 29.13, 199.01 +/- 154.01 pg/ml, respectively) when compared with the patients without invasion (0.56 +/- 1.05, 33.01 +/- 36.52 pg/ml) (P = 0.03 and 0.015). When the preoperative and postoperative serum growth factor levels were compared, the serum EGF level was found to be lower (125.93 +/- 62.84, 100.02 +/- 31.19 pg/ml, P = 0.007) and the serum IGF-1 level (165.81 +/- 153.6, 301.35 +/- 131.24 pg/ml, P < 0.001) was found to be higher in the postoperative 6-month specimens. Uveal melanomas express HGF, c-Met, EGFR, and IGF-1R. Vitreal growth factor levels and expression of EGFR and IGF-1R are correlated with some clinicopathological parameters. IGF-1 and EGF may have a role in the development and progression of uveal melanoma. Melanoma Res 20:126-132 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.