The real incidence of congenital self-healing reticulohistiocytosis (CSHR) may be underreported because of its high rate of spontaneous resolution and lack of clinical recognition. Currently, there are no criteria other than clinical that can reliably distinguish CSHR from cutaneous involvement by disseminated Langerhans cell histiocytosis (LCH). In this study we investigate the role of E-cadherin, Ki-67, and phosphorylated histone H3 (PHH3) immunohistochemical stains in distinguishing CSHR from disseminated LCH. We found that no significant difference was seen in the histologic features and the expression of E-cadherin, Ki-67, and PHH3 between the two groups; thus supporting the theory that CSHR and LCH represent different ends of a spectrum of the same condition.