Clear cell proliferations of the skin consist of a diverse group of lesions characterized by the presence of cells with abundant clear cytoplasm. They may arise from primary, metastatic, or non-neoplastic origins, with their distinctive cytoplasmic clearing attributable to causes ranging from artifact to accumulation of materials such as glycogen, mucin, or lipids. Despite the heterogeneity of these lesions, their distinguishing characteristics may be subtle, especially at high power. As such, histologic diagnosis can be challenging, and proper consideration relies on an understanding of the scope of possible origins, etiologies, and key immunohistochemical staining patterns of the various entities. This review categorizes cutaneous clear cell neoplasms by histogenesis, and offers differential diagnostic strategies to aid in their clinicopathologic evaluation.