Having already knocked out Manchester City and Arsenal this season another upset against the holders is entirely possible and the Stamford Bridge clash has set the Potteries abuzz with nostalgia.
Stoke were founder members of the Football League in 1888 yet their only-ever trophy is the 1972 League Cup when they beat Chelsea in the final.
That success came in their all-too brief "glory years" and was sandwiched by two controversial extra-time FA Cup semi-final defeats by Arsenal that still hurt to this day.
In 1971 Stoke led 2-0 at Hillsborough only for Arsenal to make it 2-2 with a penalty after a then-unheard of five minutes of injury time and win the replay 2-0 en route to the Double.
The following year they drew again - despite Arsenal having to play the last 15 minutes with striker John Radford in goal after an injury to Bob Wilson.
Stoke led in the replay only for Arsenal to level and then win the game with a goal by Radford. Local legend has it that Radford was miles offside but that the linesman mistook a white-coated programme seller for a white-shirted Stoke defender and allowed the goal.
"It beggars belief," former Stoke winger Terry Conroy recently said of the incident. "I look back on my career with no regrets apart from those two games - it would have meant so much to the club and the area."
Stoke never reached even the quarter-finals again until this season and although the Cup has nothing like the prestige it carried in those days, victory on Sunday would be huge.
At 83 years Reading's wait for a sixth-round appearance has been far longer and the only non-Premier League side left in the competition will hope to match their 1927 achievement of reaching the semis by beating visiting Aston Villa on Sunday.
Despite struggling near the foot of the Championship they have accounted for Liverpool, Burnley and West Bromwich Albion this season.
Villa, beaten in the League Cup final by Manchester United last weekend, will be desperate to secure a return to Wembley, where both semi-finals are played.
Portsmouth, adrift in the Premier League and in debt-ridden administration, can briefly forget their woes when they host Birmingham City in the first of the quarter-finals on Saturday.
The 2008 winners had a morale-boosting 4-1 win over local rivals Southampton in the last round and a place in the semi-finals would be a fitting reward for the fans who have been so impressive despite the chronic mismanagement of their club.
Fulham host eight-times winners Tottenham Hotspur in an intriguing all-London clash on Saturday when Roy Hodgson's improving side will hope to do better than at the same stage last season when they were thrashed 4-0 at home by Manchester United.
