We demonstrate the first application of the recently proposed method of optical palpation to in vivo imaging of human skin. Optical palpation is a tactile imaging technique that probes the spatial variation of a sample’s mechanical properties by producing an en face map of stress measured at the sample surface. This map is determined from the thickness of a translucent, compliant stress sensor placed between a loading element and the sample and is measured using optical coherence tomography. We assess the performance of optical palpation using a handheld imaging probe on skin-mimicking phantoms, and demonstrate its use on human skin lesions. Our results demonstrate the capacity of optical palpation to delineate the boundaries of lesions and to map the mechanical contrast between lesions and the surrounding normal skin.