The new 10mm pixel display LED screen will be positioned above the Boots and Barclays premises and aims to take advantage of the increased pedestrian areas since the closure of Glasshouse Street to traffic.
The project, managed by MT2 Limited, the company that has overseen the last five installations on the site, will start in August and the screen is due to be in operation by December.
It has not been decided whether or not just one advertiser, or more, will take over the new screen, but a spokesman for MT2 Limited said one advertiser would be preferable.
As part of the update, the strip screen known as Piccadilly Lite, which was added in 2007 and was the only site that could be booked by regular outdoor campaigns, will be removed, as will the balcony which it currently sits on.
Clear Channel Outdoor had the contract to sell short-term ad campaigns on the Piccadilly Lite site up until around 18 months ago.
McDonald's is also updating its existing screen after renewing its contract, bringing in a second-generation LED screen.
Work has already started on McDonald's 16mm pixel replacement screen, which is due to be unveiled in early October. It follows Coca Cola and Samsung updating their screens for the Olympics in 2011 and 2012.
All the signs on the Piccadilly site have been LED since February 2011. Sanyo's neon sign was the last static site to go, when Hyundai replaced the Japanese electronic manufacturer, which had owned the spot since 1978.
The new developments are the last scheduled for some years and introduction of the new screen will complete the display.
The Piccadilly Lights display has existed for more than 100 years, showcasing 50 brands including Carlsberg, Max Factor, Volkswagen and Schweppes.