The fake tweet had Medvedev saying: "I am resigning. I am ashamed of the government's actions. I'm sorry." Medvedev's office rushed to confirm his account was hacked.
Medvedev is often the butt of jokes in Russia, with some people accusing him of being the puppet of President Vladimir Putin. Using the diminutive of Putin's first name, the hacker tweeted: "I have long wanted to tell you. Vova! You are wrong!"
There was disappointment among many in Russia's Internet-savvy middle class after Medvedev stepped down from the presidency to allow Putin to return for a third Kremlin term in 2012, a decision that sparked big street protests in Moscow.