The morphology and histology of test sites commonly used to study the penetration of lip products differ significantly from those of the human lip itself. The aim of this study was to investigate whether the porcine snout could serve as an equivalent in vitro model for human lips. The lips of human test subjects and biopsies of porcine snout tissue were compared using histological and microscopic techniques. Using a dermatological laser scanning microscope, the penetration of topically applied fluorescent sodium fluorescein was investigated in vivo on human lips and in vitro on the porcine snout. Biopsies from the in vitro experiments were studied using fluorescence microscopy. Some parts of the porcine snout show a similar morphology and histology as human lips. The stratum corneum (SC) and the epidermis of the porcine snout are thicker than those of human tissue. Both in vivo and in vitro, the topically applied fluorescent dye was detected only on the skin surface and within the uppermost SC layer. These results indicate that porcine snout can be used as an in vitro model for human lips in penetration studies. Both human and porcine tissues exhibit an efficient barrier against the penetration of topically applied substances.