Measurement of cell surface expression is an essential part of studying membrane proteins. Traditional techniques for measuring surface expression depend on the availability of appropriate radioligands or antibodies towards extracellular epitopes of a protein of interest. The current protocol outlines the use of an assay to monitor surface expression of membrane proteins tagged with a bacterial β-lactamase in mammalian cell lines. The use of this technique allows for quick, quantitative, sensitive, and inexpensive measurement of surface expression, with the potential for high-throughput screening.