Cyto-architectures represent the arrangement that cells continue to maintain on cytological specimens and are the direct expression of their original anatomical organization. They can be defined as the point of connection between cytologists and histopathologists. The maintenance of the architectural pattern of cells also on cytological specimens can be very useful not only in obtaining diagnosis of neoplasia but, in many cases, also defining the histotype of that specific neoplasia. While cell’s details, such as chromatin pattern, morphology and size of nucleoli, and cytoplasmic differentiation, must be observed at high magnification, the architectural pattern of cells needs to be evaluated at low-medium magnification. In this chapter, the main cyto-architectures of skin neoplasia will be treated.