Objective To investigate the confocal laser scanning microscopic (CLSM) features of several hypopigmented diseases, including vitiligo, nevus depigmentosus, progressive macular hypomelanosis and amelanotic nevus. Methods A total of 131 patients with hypopigmented diseases were recruited in this study. CLSM was performed on depigmented lesions, adjacent normal appearing skin and lesion borders at the dermoepidermal junction level in these patients. Results CLSM showed that in progressive vitiligo, melanin was completely absent from some areas in vitiliginous skin, while some areas were present with residual dermal papillary rings which were less intact with decreased melanin content; the border of lesions was obscure; some dermal papillary rings lost integrity in normal appearing skin adjacent to the vitiliginous skin. There was a complete disappearance of pigment in vitiliginous skin, clear border of lesions and intact dermal papillary rings with bright reflected light in adjacent normal appearing skin in stable vitiligo. Dendrite-like melanocytes with bright reflected light were noted in recovery-stage vitiligo. The CLSM imaging of nevus depigmentosus and progressive macular hypomelanosis was similar: dermal papillary rings were intact with decreased melanin content and weak reflected light in depigmented lesions. No significant difference was observed in the structure of dermal papillary rings or melanin content between vitiliginous skin and adjacent normal-appearing skin of nevus anemicus. Conclusion Combined with clinical manifestations, CLSM may serve as an auxiliary tool to discriminate vitiligo, nevus depigmentosus, progressive macular hypomelanosis and amelanotic nevus.