The 30-year-old is definitely out of Thursday's Europa League quarter final against Basel at White Hart Lane.
Spurs boss Andre Villas-Boas admits he has doubts over the availability of the England international for the second leg in Switzerland.
And Villas-Boas believes the Premier League visit of Manchester City on 21 April is a realistic target for Defoe's return.
"Jermain has a muscle injury which is probably going to take him out of the next two games definitely and maybe Basel away," Villas-Boas said.
"If he can't make Basel away he should be fit for Man City.
"It's a big blow. It's on the same muscle that he had a small tear last month. It's on the other side now and it's a big miss as he represents a lot for us and he will be a big miss."