Sixteen-year-old Domenic Bassini sets out alone for America from his small village in Italy in 1914. He falls in love during a brief onboard affair with the beautiful Francesca, the wife of a man with Sicilian Mafia connections. But he loses her and arrives in Boston instead with an orphan stowaway named Ernesto Lentini in tow.

Domenic and Ernesto stay at the home of old family friends in Boston's Italian North End neighborhood, sharing a room with their son, Joe. Domenic becomes like a big brother to Joe and Ernesto, who become inseparable friends.

As the years and decades pass, youthful rivalries and fateful decisions lead to unpredictable and sometimes unsavory outcomes. Between moments of joy and great tragedy, the three friends' lives take very divergent paths amidst the turbulence of factions vying for power in the early 20th century Boston where the lines between politics, crime and policing are blurred.

But after all that has kept them apart, can Domenic, Ernesto, Joe and even Francesca, come together to settle the score with those who have spent a lifetime fighting against them?