American cyclist Joseph Dombrowski held off the rest of the breakaway pack to win the fourth stage of the Giro d’Italia on Tuesday for his first victory in a Grand Tour, and Alessandro De Marchi took the leader's pink jersey.

Dombrowski, who rides for UAE Team Emirates, attacked on the first uphill finish of this year’s race and crossed the line 12 seconds ahead of De Marchi.

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Race's overall leader Filippo Ganna pedals during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

American cyclist Joseph Dombrowski held off the rest of the breakaway pack to win the fourth stage of the Giro d’Italia on Tuesday for his first victory in a Grand Tour, and Alessandro De Marchi took the leader's pink jersey.

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Filippo Fiorelli was third, 27 seconds behind Dombrowski.

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

João Almeida was one of the favorites to win the Giro after leading the race for 15 days last year but his chances are all but over after losing more than four minutes on Tuesday.

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

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Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

It was the 29-year-old Dombrowski’s first pro win outside of the United States.

Race's overall leader Filippo Ganna pedals during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Race's overall leader Filippo Ganna pedals during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Filippo Fiorelli was third, 27 seconds behind Dombrowski.

De Marchi moved into the overall lead ahead of Filippo Ganna. He has a 22-second advantage over Dombrowski and 42 seconds over third-place Louis Vervaeke.

Ganna had led the Giro since winning the time trial that opened the race on Saturday.

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

João Almeida was one of the favorites to win the Giro after leading the race for 15 days last year but his chances are all but over after losing more than four minutes on Tuesday.

Wednesday’s fifth stage is a flat and straight 177-kilometer (110-mile) route from Modena to Cattolica on the Adriatic coast.

The Giro finishes on May 30 in Milan with an individual time trial.

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

More AP sports: https://apnews.com/apf-sports and https://twitter.com/AP_Sports

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)

Cyclists make their way during the 4th stage of the Giro d'Italia, tour of Italy Cyling race from Piacenza to Sestola, Italy, Tuesday, May 11, 2021. (Fabio FerrariLaPresse via AP)