It was no small hit either. Ramirez's three-run blast to the opposite field in right field against Miguel Batista instantly turned a three-run deficit into a tie game. The Red Sox eventually lost the game, 4-3.
The game-tying homer perked up Red Sox manager Terry Francona, who had been ejected just moments earlier.
"What a nice swing," Francona said. "I saw it on TV. But what a nice swing. We were pretty quiet offensively up to that point. He gets us right back in the game."
The next time Ramirez goes deep, he will become the 24th player in Major League history to hit 500 homers.
Before coming through with that clutch blast, Ramirez had been homerless in his last 45 at-bats. It was his first long ball since May 12 at Minnesota.
Though he has been chatty of late, Ramirez didn't feel like discussing the homer after Boston lost in walk-off fashion.
"Don't worry about it," Ramirez said before heading off to the player's lounge.
Ramirez's teammates know that his next homer will be something special.
"It's good, it's good for him," said Red Sox catcher Jason Varitek. "Once he gets it past him, he'll be able to just keep going. It's been a little while for him, but he's been swinging the bat well the last three or four games."
As he began his trot around the bases, Ramirez raised his right arm in triumph. Safeco Field has been an eventful venue for Ramirez over the years. In 2002, Ramirez fractured his left index finger at Seattle when he dove headfirst into home plate. On May 15, 2005, Ramirez smashed career homer No. 400 at Safeco.
In fact, Ramirez has had quite a bit of success against the Mariners. This was his 38th homer lifetime against Seattle, his fifth most against any opponent.
The left fielder got off to a quick home run start this year, hitting six homers in the first 19 games.
He now has nine home runs on the season.
Before the game, Ramirez was in a playful mood, asking one reporter if the Red Sox were going to pick up his option for next season and quizzing another if he had a chance to win the Gold Glove Award.
Ian Browne is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.