NOTCH1 is a transmembrane receptor, which plays a role in cell fate determination, growth, and survival. Activating NOTCH1 mutations are common in T-cell lymphoblastic leukemia and lymphoma. Simple variants in NOTCH1 are seen in about 6% of all tumors, including 13% of head and neck tumors and 9% of skin tumors. Multiple targeted agents of the NOTCH pathway are being developed.