This chapter presents a state of the art summary of blastic plasmacytoid dendritic cell neoplasms (BPDCN) in relation to its biology, epidemiology, disease mechanisms, clinical signs, diagnosis, treatment and prognosis. The cutaneous tropism of BPDCN tumor cells is highlighted by their expression of antigens that favor skin migration and by their expression of chemokine binding cognate receptors. BPDCN is a rare, aggressive hematologic malignancy, accounting for 0.44% of all hematological malignancies, lesser than 1% of acute leukemias, 0.7% of cutaneous lymphomas, and 6.3% of the NK-cell lineage malignancies. Risk factors for BPDCN include viral infection, prior chemotherapy, and other myeloid neoplasms. The BPDCN leukemic variant is characterized by an elevated white blood cell count, circulating blasts, and massive bone marrow infiltration along with a localized or generalized lymphadenopathy, splenomegaly, hepatomegaly, multiple skin lesions, anemia, and thrombocytopenia. Patients suspected of BPDCN should undergo blood cell counts and a skin/bone marrow biopsy to demonstrate characteristic cell morphology and specific immunophenotype.