In varicella the distribution of the lesions over the surface is far more erratic than in smallpox. The very decided tendency to grouping of lesions upon the face and about the wrists so characteristic of smallpox does not occur in varicella, in which the vesicles may appear even more extensively on the trunk than upon the face. In varicella the palms and the soles, except in infants, are almost never affected; while in smallpox these regions are practically never exempt. It is true that in the extraordinarily mild cases of smallpox, such as have constituted the majority of cases during the past two years throughout the West, lesions may or may not be present on the palms and soles; but in the severe and moderately severe cases, such as have characterized the recent epidemic in New York, the soles and especially the palms have practically without exception shown the lesions. The localization of smallpox lesions on the palms and soles deserves far more emphasis than is generally accorded it in the textbooks, many of which even fail to mention it all. It may be put down as a safe rule that a case showing an extensive eruption of vesicles or pustules, however suspicious in other respects, is not smallpox if the palms and soles are free. *Acne.*--Among the skin diseases proper there are a few whose appearance upon hasty examination may occasion some confusion with smallpox. Acne pustulosa presents only a superficial resemblance to variola, but in cases where it is accidentally associated with an acute febrile disease, like grippe, for instance, it may give rise to some diagnostic difficulty. In these cases, however, inquiry will develop the fact that the acne lesions have been present before the inception of the febrile disease; and the presence of comedos, the limitation of the lesions to the face, chest, and back, together with the absence of any lesions on the palms and soles, will serve to exclude smallpox. *Impetigo Contagiosa.*--In impetigo contagiosa there might under similar circumstances be a momentary doubt as to the nature of the illness. Impetigo lesions have no typical distribution on the surface, the mucous membranes are always exempt; the vesicle itself is extremely superficial, ruptures very readily, and is at once replaced by a crust, so that lesions in various stages, vesicles, pustules, and crusts may always be seen at the same time.