The study of expressed proteins in neoplasia is undergoing a revolution with the advent of proteomic analysis. Unlike genomic studies where individual changes may have no functional significance, protein expression is closely aligned with cellular activity. This perspective will review proteomics as a method of detecting markers of neoplasia with a particular emphasis on lung cancer and the potential to sample the lung by exhaled breath condensate (EBC). EBC collection is a simple, new, and noninvasive technique, which allows sampling of lower respiratory tract fluid. EBC enables the study of a wide variety of biological markers from low molecular weight mediators to macromolecules, such as proteins, in a range of pulmonary diseases. EBC may be applied to the detection of lung cancer where it could be a tool in early diagnosis. This perspective will explore the potential of applying proteomics to the EBC from lung cancer patients as an example of detecting potential biomarkers of disease and progression.