Inorganic ultraviolet filters such as titanium dioxide (TiO2), safe to use on healthy skin, are often applied on compromised and irradiated skin. The aim of this study was to evaluate in vitro the cutaneous penetration of TiO2 nanoparticles (≥ 20 nm primary size), included in a sunscreen, in intact, damaged, irradiated, and damaged/irradiated pigskin. Cutaneous penetration and localization of TiO2 after a 24-h sunscreen application were investigated quantitatively using inductively coupled plasma-mass spectrometry, and qualitatively using transmission electron microscopy (TEM). Elemental identity of the nanoparticles was evaluated by TEM-coupled Energy Dispersive X-ray analysis (TEM-EDX). In intact and damaged/irradiated skins, 102.35 ± 4.20% and 102.84 ± 5.67% of the titanium deposited, respectively, were found at the surface and stratum corneum (SC), whereas only 0.19 ± 0.15% and 0.39 ± 0.39% were found in the viable epidermis and dermis and no titanium was detected in the receptor fluid. TEM-EDX analysis confirmed the presence of titanium in the aggregates formed by TiO2 at the SC surface, as already characterized in the sunscreen formulation. TiO2 nanoparticles included in a sunscreen thus remain in the uppermost layers of the SC, whether in intact skin or in compromised and/or skin exposed to simulated solar radiation.