The use of non-invasive imaging techniques in dermatology has been reported to improve the diagnostic accuracy and the practice of biopsies, and at the same time to reduce the need for tissue excision. However, the current clinically-available imaging techniques do not yet entirely meet the need for early and accurate, non-invasive detection of all skin cancers. A handheld line-field confocal optical coherence tomography (LC-OCT) device has been designed for high-resolution non-invasive imaging of human skin, in vivo. LC-OCT delivers tomographic images in real-time (10 frames/s) with a quasi isotropic spatial resolution of ~ 1 μm, revealing a comprehensive morphological mapping of skin tissues at a cellular level, down to a depth of ~500 μm. The device has been applied to the in vivo imaging of various skin lesions. Surgical excisions of the lesions have then been performed followed by tissue processing to realize H&E-stained histopathological images. The spatial resolution, orientation, and imaging contrast mechanism of the LC-OCT images have allowed for a good level of similarity with the conventional histopathological images. LC-OCT was able to show most of the histopathological elements that allow for medical diagnosis. Using handheld LC-OCT as an adjunct tool in dermatology could help improve clinical diagnostic accuracy, allowing for the early detection of malignant skin tumors and a reduction in the number of surgical excisions of benign lesions.