Agranular CD4/CD56 hematodermic neoplasm (CD4/CD56 HN), also termed blastic natural killer cell lymphoma, is characterized by a peculiar immunophenotype and high skin tropism. The lineage of origin is not known, and a plasmacytoid dendritic cell derivation has been proposed. CD4/CD56 HN generally is diagnosed by using tumor skin biopsy, with the most important differential diagnosis being myelomonocytic leukemia cutis. We evaluated the expression of 2 plasmacytoid dendritic cell antigens, T-cell leukemia 1 (TCL1) and cutaneous lymphocyte-associated antigen (CLA), in 29 cases of CD4/CD56 HN and 18 cases of myelomonocytic leukemia cutis. TCL1 and CLA were expressed in 26 (90%) of 29 CD4/CD56 HN cases vs TCL1 expression in 3 (17%) and CLA expression in 14 (78%) of 18 leukemia cutis cases. Furthermore, CLA antiserum displays a peculiar small-dot staining pattern in CD4/CD56 HN. These results suggest that TCL1 and CLA are good markers for CD4/CD56 HN tumor cells and add support for a plasmacytoid dendritic cell origin. The high skin tropism of CD4/CD56 HN might be related to the skin-homing property of CLA.