Tipifarnib, a farnesyltransferase inhibitor, impedes the activation of oncogenic HRAS by preventing its translocation to the plasma membrane and subsequent downstream effector signaling.(14) Using targeted exome sequencing data we show that HRAS-mutant cancers are associated more commonly with co-mutations of genes encoding effectors in the MAPK and PI3K pathway than tumors driven by KRAS or NRAS, with specific lineage differences. The gene discussed is HRAS; the disease is cancer.