Summary Uveal melanoma ( UM ) is a rare ocular tumor that may lead to deadly metastases in 50% of patients. A disintegrin and metalloproteinase ( ADAM )10, ADAM 17, and the HGF ‐receptor c‐Met support invasiveness in different tumors. Here, we report that high ADAM 10, MET , and, to a lesser extent, ADAM 17 gene expression correlates with poor progression‐free survival in UM patients (hazard ratio 2.7, 2.6, and 1.9, respectively). About 60% of primary UM expresses c‐Met and/or ADAM 10 proteins. Four UM cell lines display high levels of ADAM 10 and ADAM 17, which constitutively cleave c‐Met, inducing the release of soluble c‐Met. ADAM 10/17 pharmacological inhibition or gene silencing reduces c‐Met shedding, but has limited impact on surface c‐Met, which is overexpressed. Importantly, ADAM 10 silencing inhibits UM cell invasion driven by FCS or HGF , while ADAM 17 silencing has a limited effect. Altogether our data indicate that ADAM 10 has a pro‐invasive role and may contribute to UM progression.