NRAS encodes neuroblastoma RAS viral oncogene homolog, which has intrinsic GTPase activity. NRAS activation by growth factors stimulates multiple effector pathways such as RAF and PI3K to promote cell proliferation. Simple variants in NRAS are seen in about 5% of all tumors, including 15% of skin tumors, 7% of thyroid tumors, and 4% of colorectal tumors. Mutations in NRAS predict resistance to EGFR inhibitors in non-small cell lung cancer (NSCLC) and colorectal cancer. Preclinical models suggest that MEK inhibitors may be effective in NSCLC. Early clinical data suggest that MEK inhibitors may be effective in melanoma with NRAS variants. Thyroid tumors with NRAS variants may be sensitive to MEK inhibition in combination with radio-iodine.