The lack of understanding of the mechanical behavior of the human skin layers makes the development of drug delivery using microneedles or microjets a challenging task. In particular, the key mechanical properties of the epidermis composed of stratum corneum and viable epidermis should be better understood. Micro-indentation experiments were applied, using a spherical tip with a large diameter to the sample thickness ratio. The Young's moduli were derived via an analytical and a numerical method. The tests showed that the analytical method was not appropriate to assess the Young's moduli. That is why a numerical model was used to obtain the correct stiffness. When loaded perpendicularly, the stiffness of both the epidermis and stratum corneum vary between 1 and 2 MPa. No significant differences in stiffness between the stratum corneum and viable epidermis were observed. (C) 2011 Elsevier Ltd. All rights reserved.