The idea that skin disorders following Blaschko lines represent genetic mosaicism is widely accepted. It seems likely that the two skin types represent the two different genotypes, but this has been remarkably difficult to prove, most studies showing a mixture of cell types in biopsies from both types of skin. Only for linear epidermolytic hyperkeratosis has it been possible to show mutant cells confined to the abnormal streaks. The hypothesis proposed here to explain this paradox is that disorders following Blaschko lines are due to mutations in genes expressed in epidermal cells (keratinocytes and melanocytes) rather than in dermal fibroblasts. The work on epidermolytic hyperkeratosis used keratinocytes, whereas most studies have used skin fibroblasts. Almost all disorders following Blaschko lines are epidermal: inflammatory, dysplastic, dyskeratotic, appendage-related, or pigmentary, and the remainder can be explained on the basis of epidermal influences on the dermis. If this hypothesis is correct, it points to a useful model system for elucidating the genetic component of common dermatoses sometimes found in Blaschko lines namely eczema, psoriasis, lichen planus, and vitiligo.