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Elastic scattering spectroscopy (ESS) has shown to be a useful technology for determining morphological changes associated with the progression of intra-epithelial neoplasia; however, the origins of differences seen in ESS spectra with the progression of disease is not well understood. We use a two-layer tissue model to study the effects of nuclear size and density on ESS spectra collected via an optical fiber probe. The presence of various sizes and densities of epithelial nuclei distort the diffuse reflectance spectrum; however, information regarding the nuclear size and density is preserved.