In CRC, Notch1 and Notch2 have opposite roles in determination of the tumor biological behavior; Notch1 and Notch2 are independent adverse prognostic predictors, with a synergistic effect of positive Notch1 and negative Notch2 co-expression on predicting poor overall survival [4,183,184]. The gene discussed is NOTCH1; the disease is colorectal carcinoma.