Cumulative evidence suggests that ~20% of ACC tumors carry mutations in NOTCH1, a critical regulator of cell proliferation, differentiation, and survival [7, 8, 14, 15], and that ACCs with alterations involving portions of NOTCH1 encoding the NRR and PEST domains are associated with worse prognosis [7, 8, 15, 72, 74, 75]. Here, NOTCH1 is linked to adrenal cortex carcinoma.