Ahead of the 2012–13 season, Italian club Milan were interested in signing Papadopoulos. After showing interest, Schalke accused Milan of making an illegal approach for Papadopoulos without the club knowing. Also interested were Russian giants Zenit Saint Petersburg, but when their £16 million bid for Papadopoulos was accepted by Schalke, Papadopoulos rejected the move, opting to stay in Germany. In September 2012, Papadopoulos signed a new contract with Schalke that will keep him at the club until 2016. On matchday two of the 2012–13 season, Papadopoulos scored his first goal of the season, and third in the Bundesliga, in a 3–1 win over FC Augsburg. A virus, however, would later kept him out of play for a number of games, and he would later undergo surgery in an attempt to correct a knee injury he suffered in a 3–1 loss away at Hamburger SV in November 2012.