While previous studies show a role of DVL2 silencing in proliferation in vitro, our report herein for the first time showed the depletion of DVL2 along with in vitro HER2 inhibition by neratinib, clinically approved HER2 inhibitor, shows an additive anti-cancer effect in two HER2-overexpressed breast cancer cell lines, BT474 and SKBR3. The gene discussed is DVL2; the disease is breast carcinoma.