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There is currently no standard screening technique for oral cancer and its precursors other than visual identification and biopsy of suspicious lesions. To aid noninvasive early detection of oral neoplasia in vivo, we previously developed a molecular-specific contrast agent targeted against epidermal growth factor receptor. Here, we present a simple fluorescence spectroscopy system to detect the presence of this contrast agent in biological models representative of living tissues in order to demonstrate the feasibility of using a spectroscopy system in conjunction with a contrast agent as a screening technique for oral cancer. The spectroscopy system was tested for the ability to detect the contrast agent in four in vitro models: multilayer tissue phantoms made of cells pre-labeled with the contrast agent, multilayer tissue phantoms labeled with the contrast agent from the surface in conjunction with a permeability enhancing agent, fresh tissue slices from normal and abnormal oral cavity biopsies, and whole normal and abnormal oral cavity biopsies. The optical signal from samples labeled with the contrast agent was 3--32 times stronger compared to controls and was detected with a signal-to-noise ratio greater than 10. These results demonstrate that an inexpensive and simple spectroscopy system can be used in biological models of living systems to detect the optical signal from a contrast agent targeted toward a cancer-related biomarker with good signal-to-noise ratios. Coupling inexpensive fluorescence spectrometers with molecular-specific contrast agents has the potential to improve the early detection of oral neoplasia by providing a low-cost screening tool.