Two injury-time goals gave Sporting Lisbon a 2-0 victory over Spurs in the group stage of the European competition.
Spurs had a number of good chances but couldn't take them and were on the verge of getting a point.
Paulinho headed in from the left-wing corner to give the hosts the lead in the last minute of the game.
It got better forSporting as another substitute, Arthur Gomes, hit a fine, low strike to make it 2-0 and handSpurs their first loss of the season.
After two victories, Sporting are top of the group with six points, followed by Spurs with three and Eintracht Frankfurt with two.
For the first time in their eight matches this season, Spurs could not find a goal, despite Ruben Amorim's claims that they were one of the best attacks in the world.
Richarlison scored twice in a 2-0 home victory over Marseille last week and he had a number of chances to score.
He had a chance to put the ball in the net in the first half, but his shot was blocked and he was ruled to be in an area where he wasn't.
Richarlison had two chances in the second half, but both times he failed to score.
Spurs dominated the start of the second half against their hosts in the Portuguese Primeira Liga.
Kane's powerful strike was parried by Adan, who also made an excellent stop at full stretch to save Royal's second shot. Kane was unable to get on the end of Ivan Perisic's excellent low cross.
Spurs' missed chances proved costly as they lost their second Group D game of the season, a 2-0 defeat to Sporting.
When he was a teenager, he was compared to Lionel Messi by Mauricio Pochettino, who was the Spurs boss at the time.
He moved to Lisbon in the summer after leaving north london.
He was a constant threat with his dribbling ability and he scored one and made one in the first round of the European competition.
Pedro Goncalves, an ex-Wolves player, was set up by him after seven minutes.
It would have been one of the goals of the season if Lloris hadn't made a great save to keep out a superb run by Edwards in the first half.
It was the late goals from Paulinho and Gomes that made the difference in the game.