Contractor Taylor Woodrow has left the £100m mixed-use Cube development in Birmingham.
The 17-storey scheme, designed by Make architects, is likely to be hit by delays as the contract must now be retendered.
Client Birmingham Development Company confirmed that Taylor Woodrow had left the scheme, but the reasons for the departure remain unclear.
Taywood was due to start on site by the end of the year and had moved workers in to the project office in the neighbouring Mailbox development.
The scheme, which was supposed to be complete by 2008, is eagerly anticipated in Birmingham. The residential element has broken sales records and is being let at the highest price per square foot ever charged in the city.
Sir Robert McAlpine and Miller declined to comment on whether they would retender for the scheme.
The Cube also includes Birmingham's first rooftop restaurant, a hotel, waterside cafes, designer retail stores, offices and apartments.
Taylor Woodrow declined to comment.