Targeted therapy utilizing selective MEK inhibition appears promising for uveal melanoma based on preliminary results of a phase II clinical trial; however, a subset of patients with GNAQ/11 mutation are resistant to this therapy.12,24 It has been suggested that the resistance is due to existence of a unique subset of “MEK-resistant genes” in a subset of GNAQ mutant tumors.12 Our findings provide another possible explanation and suggest that tumor heterogeneity and variability of MAPK activation could be an important cause for therapy resistance. The gene discussed is MAP2K7; the disease is uveal melanoma.