To evaluate the potential of a new in vivo confocal Raman microprobe, we undertake a pilot study in human skin. A fiber optic probe is operated with a laser and trials are conducted in healthy volunteers. We examine changes in molecular composition and structure of the stratum corneum, from different volunteers, from different anatomical sites and skin layers. Main spectral variations are detected in the following regions: (amino acids); (proteins); and , , and (lipids). Curve fitting of the amide 1 region performs in detail protein secondary structural variations of the amide 1 band. Protein conformation is also found to vary depending on the anatomical site and volunteer. Similar analysis of the spectral window reveals a different organization of lamellar lipids: gel for forearm and palm, and liquid-crystalline phase for fingertips. All these variations result from changes in the stratum corneum components such as natural moisturizing factor (NMF), lipids (namely ceramides), and water. Hierarchical clustering classification is also performed to sort out Raman data obtained from different subjects. Further improvement of the confocal probe would be to adapt a configuration enabling access to other anatomical sites.