Twin-twin transfusion syndrome (TTTS) is present in approximately 5-15% of monochorionic-diamniotic twin pregnancies. A chronic blood flow imbalance through placental vascular anastomoses from the donor to the recipient twin is considered the pathophysiologic mechanism responsible for the development of TTTS. Discordant echogenicity between the donor and recipient placenta has been proposed in a previous case report as an additional sonographic sign of TTTS. Here, we present a case of TTTS with discordant placental echogenicity characterized by a hyperechoic and thicker placental side in the donor twin associated with reduced vascular Doppler signals, histologic lesions suggestive of ischemic changes, and overexpression of anti-angiogenic factors.