England striker Defoe, who has scored 143 goals in two spells with Spurs, is about to complete his move to Toronto in the MLS.
A hamstring strain means the 31-year-old will miss the chance to sign off with another goal at White Hart Lane, but he will be on the pitch at half-time of the Europa League last-32 clash with Dnipro to say his goodbyes.
Sherwood said: "Jermain Defoe is, possibly along with Jimmy Greaves, one of the best goalscorers this club has ever seen.
"Let's hope we can find another one like Jermain Defoe because he is all about goals and he always played with all his heart whenever he put on the shirt.
"Everyone appreciated his efforts and he certainly is a legend at this football club."
Spurs defender Kyle Naughton added: "He has been great for us since I have been here.
"He has been great to play with. You just gave him the ball and let him do the business. He will be missed."
Defoe's absence means the goalscoring duties will once again fall to Emmanuel Adebayor and the much-maligned Roberto Soldado.
Spaniard Soldado missed an open goal in Spurs' 1-0 first-leg defeat in Ukraine and has found the net just once in his past 11 appearances.
"Robbie knows his time has come and hopefully that will be tomorrow (Thursday)," added Sherwood.
"We know what he can do, he is a top player otherwise he would not be at the club. Now is the time for one to ricochet off his backside and go in and then he can go on a run like Adebayor has.
"It would be handy if the two of them were scoring."
Sunday's 1-0 defeat by Norwich, on the back of their reverse in Ukraine, left Spurs six points adrift of Liverpool in the race for a top-four finish.
But Sherwood refuses to use the gruelling Europa League campaign as an excuse for their domestic wobbles and insists it would not be a blessing in disguise if they bowed out of the competition on Thursday.
"I wouldn't use it as an excuse but the facts are our record isn't fantastic after games in Europe," he said..
"But we want to progress in this competition, it means a lot to us. We are not blessed with trophies recently.
"It's a long competition. On quality you have to say the Champions League is hardest, but on endurance you have to say it's the Europa League. It is sapping.
"It was always going to be tough to get into the top four, there are more teams than ever fighting for it. But we know we still have an opportunity.
"If we beat Cardiff on Sunday and Liverpool lose at Southampton, then we still have to go to Anfield so you never know.
"But, with respect, if you can't beat Norwich away you don't deserve to be in the Champions League."