Here, we observed greater activation of the Rho/MRTF pathway in SK-Mel-147 and other NRAS mutant melanoma cells compared to the BRAF mutant SK-Mel-19 cells, as measured by stress fiber formation, nuclear localization of MRTF-A/B, and mRNA expression levels of the MRTF-target gene, CYR61. Importantly, Rho/MRTF pathway activation correlates strongly with intrinsic resistance to trametinib in these NRAS mutant cell lines. Here, MRTFA is linked to melanoma.