He faced State Representative Randy J. Johnson and Milton V. Bauguess in the Republican primary, and he received endorsements from then-Governor Jeb Bush and then-Lieutenant Governor Toni Jennings.

Lee declared, "I have proven time and time again over a decade of being in the Senate that I can stand independent of my contributors on issues that are important to the consumers of Florida," while noting, "Let's just say, in a variety of ways, [Johnson's] campaign is taking great liberties with the truth, particularly with his so-called commitment not to take insurance money.

"[3] Ultimately, Lee won out over his opponents by a wide margin, receiving 57% of the vote to Johnson's 37% and Bauguess' 6%, and advanced to the general election, where he faced Alex Sink, the Democratic nominee.

Sink attacked him for failing to properly address property insurance during his time in the legislature and managed to rack up endorsements from a majority of the newspapers in the state,[4] including the Florida Times-Union, which praised Sink for exceeding the qualifications for the job, while criticizing Lee for failing to meet them.

He faced State Representative Rachel Burgin in the Republican primary, and a divisive election occurred, with a group allied with Burgin comparing Lee to Hillsborough County Property Appraiser Rob Turner, who was "embroiled in a porn scandal" in advertisements that were condemned by the Republican Party of Florida.

Advancing to the general election, Lee faced Elizabeth Belcher, a retired Internal Revenue Service investigator and the Democratic nominee.