Leukemia cutis (LC) is a nonspecific term used for cutaneous manifestations of any type of leukemia. LC has a wide range of cutaneous manifestations, which can make it difficult to clinically distinguish LC from other skin lesions. Patients with LC usually have concomitant systemic leukemia, but occasionally skin involvement precedes the involvement of the bone marrow or peripheral blood. Thus, a skin biopsy can be the first indication of the presence of leukemia in a subset of patients. The immunophenotyping of routinely processed skin biopsy specimens is very useful in establishing the diagnosis of LC. Although the molecular mechanisms explaining the pathogenesis of LC are not well defined, chemokine receptors and adhesion molecules may have an important role in skin tropism. We review the literature and recent advances pertaining to LC, with special emphasis on the immunohistochemical assessment and possible mechanisms involved in skin tropism by leukemic cells.