A method for examining skin tissue of a subject based upon in vivo skin imaging includes a harmonic generation microscopy (HGM) device. The HGM device is configured for observing the skin tissue and forming sectioned images of the skin tissue of second harmonic generation (SHG), third harmonic generation (THG), or combination of the SHG and the THG of an excitation light scanning the skin tissue. The method further includes a step to determine whether the morphological feature of the skin tissue is related to a skin disease.