Skin produces volatile organic compounds (VOCs) released to the environment with emission patterns characteristic of climatic conditions. It could be thought that these compounds are intermediaries in cell metabolism, since many intermediaries of metabolic pathways have a volatile potential. In this work, using gas chromatography, we answered the question of whether VOC profiles of primary cultures of human dermal fibroblasts were affected by the type of culture conditions. VOCs were determined for different types of culture, finding significant differences between skin cells grown in classical monolayer culture -2D- compared with 3D matrix immobilized cultures. This indicates that VOC profiles could provide information on the physiological state of skin cells or skin.