Aiyegbeni Yakubu, the striker Steve McClaren signed for pounds 7.5?million when in charge at Middlesbrough, haunted the Derby manager by coming off the bench to score the goal that took Reading into the quarter-finals.
The 32-year-old Nigerian striker, a deadline-day free signing from the Qatar club Al-Rayyan, used his strength to hold off Derby defenders before sweeping the ball home with eight minutes remaining.
"As soon as I saw that big smile as he was preparing to go on, I knew we could be in trouble," McClaren said. "He only needs one opportunity. His first touch was excellent, his second even better - only he can finish like that. It was a typical Yakubu goal."
McClaren was consoled by the performance of his Championship high-fliers, who came from behind to equalise after losing defender Stephen Warnock to a red card in the first half.
He said: "I'm disappointed to have lost because we wanted to be in the next round, even though we were never going to win the
FA Cup. But I can't fault the performance. It is hard to win a game when you are down to 10 men for so long but the players were heroic."
Hal Robson-Kanu had put Reading ahead when he curled in a shot early in the second half. Derby drew level eight minutes later when Darren Bent continued his remarkable run in the Cup by scoring for a sixth consecutive game in the competition. It was his fifth goal in as many matches for McClaren's side, with whom he will remain on loan from Aston Villa for the remainder of the season because there is no recall clause in his agreement.
McClaren had gambled by making seven changes to the side who took a point away to Bournemouth in Tuesday's top-of-the-table Championship clash, although an injury ruled out leading scorer Chris Martin while Tom Ince was Cup-tied.
After a bright Derby start, a clever free-kick routine presented Reading with their first clear chance. After Warnock had conceded a foul 20 yards out, Simon Cox ran up as if to strike the ball but stepped over it and instead positioned himself to receive it from Nathaniel Chalobah on the right. With Derby's defence wrong-footed he had a clear view of Kelle Roos's goal but clipped his shot against the outside of a post.
Goalkeeper Adam Federici kept Reading in the game in the first half, with saves from Bent, Jesse Lingaard, Simon Dawkins and Craig Bryson, but the dismissal of Warnock changed the balance of the tie.
Booked, a little harshly, for the foul on Robson-Kanu that set up the free-kick chance for Cox, Warnock lunged into Jamie Mackie inside the Reading half, committing a foul that was much more worthy of a yellow card and, by consequence, a red.
Reading soon found space to exploit if they could break quickly from defence and took advantage nine minutes into the second half when Chalobah's pass launched an attack along the right flank that had Derby on the retreat.
Cox and Stephen Kelly combined before the former found Robson-Kanu just inside the box. The midfielder, who scored Reading's late winner at Cardiff City in the fourth round, moved the ball on to his left foot and curled a shot out of Roos's reach.
Derby's equaliser was well deserved, if fortunate, as a shot from Lingard that was going wide struck Bent on the thigh and diverted into the net.
Yakubu dashed Derby's hopes after replacing Mackie with 20 minutes remaining. He showed his strength on the ball and eye for goal were still intact as Robson-Kanu's pass sent him charging towards the Derby goal and he kept balanced enough to sweep the ball past Roos.
"We knew what we were getting when we signed him," Steve Clarke, the Reading manager, said. "When he gets a chance like that, you expect him to score."