In the context of cutaneous carcinoma diagnosis based on in vivo optical biopsy, Diffuse Reflectance (DR) spectra, acquired using a Spatially Resolved (SR) sensor configuration, can be analyzed to distinguish healthy from pathological tissues. The present contribution aims at studying the depth distribution of SR-DR-detected photons in skin from the perspective of analyzing how these photons contribute to acquired spectra carrying local physiological and morphological information. Simulations based on modified Cuda Monte Carlo Modeling of Light transport were performed on a five-layer human skin optical model with epidermal thickness, phototype and dermal blood content as variable parameters using (i) wavelength-resolved scattering and absorption properties and (ii) the geometrical configuration of a multi-optical fiber probe implemented on an SR-DR spectroscopic device currently used in clinics. Through histograms of the maximum probed depth and their exploitation, we provide numerical evidence linking the characteristic penetration depth of the detected photons to their wavelengths and four source–sensor distances, which made it possible to propose a decomposition of the DR signals related to skin layer contributions.