The aim of this paper is to determine the best optical-probe geometry that would help to detect neoplastic lesions in oral epithelial tissue. Two Geometrical configurations are investigated. The first one implements different distances between the illumination and collection fibers, and the second one implements different fiber diameters. Both of these geometries are evaluated for their collection efficiency and depth resolution. The effect of numerical aperture (NA) and tissue optical properties on the fluorescence signal are also studied. Optical properties of dysplastic tongue epithelial multi-layered tissue were used as an input for Monte Carlo simulation. The results show that the sensitivity to superficial layers can be achieved using small fiber diameters. On the contrary, the sensitivity to deeper layers can be achieved using larger distances between illumination and collection fibers.