The Williams sisters will hold another family reunion on centre court at the US Open after registering wins on Monday that set up a tiebreaking, sibling clash in the quarter-finals at Flushing Meadows.
Fourth seed Serena routed French wildcard Severine Bremond 6-2 6-2, while seventh-seeded elder Venus crushed Agnieszka Radwanska, of Poland, 6-1 6-3 to book the rendezvous.
The sisters are 8-8 in head-to-head matches during their career and 5-5 against each other on the grand slam stage so this one will bring bragging rights as well as a slot in the semi-finals of the year's last major championship.
"It's tough to play her because she is so good," said Venus, who won their last collision at this summer's Wimbledon final for her fifth singles title at the All England Club.
Serena rued the fact that the meeting between the two twice Open champions is coming so early in the championship.
"It sucks," Serena said. "Even the semi-finals would have been better than the quarters, but at least one of us will make it to the semi-finals."
Rafael Nadal was one step away from his first semi-final in New York after taking his turn at shooting down one of the big-hitting young guns at the Open to ride into the quarters.
The Spaniard, the top-seeded world number one for the first time at a major, dodged a bevy of bullets from 20-year-old American Sam Querrey, before capturing a 6-2 5-7 7-6 6-3 win.
In the last eight, Nadal meets unseeded American Mardy Fish, who beat 32nd seed Gael Monfils, of France, 7-5 6-2 6-2.
British sixth seed Andy Murray, 21, stormed into the quarters for the first time with a 6-1 6-3 6-3 demolition of Swiss 10th seed Stanislas Wawrinka.
Murray next goes against Argentine 19-year-old Juan Martin Del Potro, who reached his first grand slam quarter 6-3 6-4 6-3 over Japan's 18-year-old Kei Nishikori in another tilt that underlined the advance of powerful young players on tour.
Arranging another women's quarter-finals date were a worn out Dinara Safina and Italy's Flavia Pennetta.
Safina had enough pep to beat Germany's Anna-Lena Groenefeld 7-5 6-0. Pennetta, the 16th seed, routed former world number one Amelie Mauresmo 6-3 6-0.
The prospect of another Williams sisters showdown had the feel of a New York heavyweight clash. Serena has dropped just 14 games from her four matches, and Venus has lost 15.
"I feel like I can win the tournament if I play my best tennis and I don't feel like I've played my best yet," said Serena.
Venus, who won their last Open encounter in the fourth round in 2005, said Serena is rounding into form.
"We're usually practising side by side, so she looks pretty consistent, like she's really working on her game," said Venus, who partnered Serena in Beijing for their second Olympic doubles title.
The Williams sisters, the only women left in the draw with any grand slam singles titles, were headed for a likely prime-time showdown at Arthur Ashe Stadium today.
Nadal said he hoped he had got his "bad day" out of the way at the Open against Querrey, who blasted in 20 aces and belted 52 winners before succumbing to the Spaniard.
"In every tournament you have one bad day, that's the normal thing," Nadal said.
"When you are playing not your best, the important thing is to win. I did today."
Nadal's tally of unforced errors was unusually high at 41, and his six double faults outnumbered his five aces.
Yet when the dust cleared on a windy day at Arthur Ashe Stadium, Nadal had outgunned Querrey and matched his best Open showing by reaching the last eight.
The future is now for the Spaniard, who has won 42 of his last 43 matches to extend a big event streak that has brought him French, Wimbledon and Olympic titles. He is aiming for his first grand slam triumph on hard court.
Women's quarter-final: Dementieva beat Schnyder 6-2, 6-3.