Cromwell sprinted to victory in the 98km stage around Lake Iseo ahead of Maria Confalonieri (Lensworld-Zannata) and Aude Biannic (Poitou-Charentes.Futuroscope.86) in third.
"It was really fast with a lot of fighting," said Cromwell. "We just tried to control it and keep the pace really high. We started quite early but our team could maintain the speed and it was less stressful for me than having to fight everyone to stay on the wheels of my team."
Cromwell launched with 200m to go and even she thought she'd launched too early.
"As I started my sprint I looked up and saw 200m to go and thought 'uh oh'!" she said. "But I had a lot of speed and only in the last 50m I could feel people near me."
Cromwell isn't known as a sprinter, with her previous Giro Rosa victory in 2012 coming at the end of a long solo breakaway.
"I don't really consider myself a sprinter but more a jack of all trades. I know I have a bit of a kick at times but it's more I knew my form was good coming into the Giro Rosa."
The shape of the overall classification remained unchanged, with Evelyn Stevens (Boels-Dolmans) retaining the maglia rosa ahead of the mountainous fifth stage of the race from Grosio to Tirano. While only 77km, the stage promises ferocious racing and an ascent of the iconic Mortirolo climb.