Background: CD2⁻ CD4⁺ CD56⁺ lymphoid malignancy has been only rarely reported the last 5 years. It is characterized by a high incidence of cutaneous involvement, cytologically agranular cells, aggressive clinical course, and negative Epstein-Barr virus (EBV) involvement. Observation: We describe a Japanese patient with a unique hematolymphoid malignancy characterized by an involvement of skin, nasopharyngeal region, bone marrow, lymph node, and a CD4⁺ CD43⁺ CD56⁺ CD2⁻CD3⁻CD8⁻ and terminal deoxynucleotidyl transferase phenotype. Clinically, the cutaneous eruptions were purplish, hard, multiple nodules. Histologically, a massive proliferation of atypical pleomorphic cells with medium-sized nuclei were observed throughout the dermis. No clonal rearrangement of T-cell receptor (TCR)-β gene or immunoglobulin heavy chain J gene was found, and no positive identification of EBV by in situ hybridization for EBV-encoded small nuclear RNA was found. The patient underwent high-dose chemotherapy with autografting of peripheral blood stem cells; however, the tumors quickly relapsed. Conclusion: We gathered data from 17 cases of lymphoid malignancy from the literature sharing immunophenotypic and genotypic features similar to those of our case, including CD2⁻CD4⁺CD56⁺ and germline rearrangement of TCR. Although the cellular origin could not be decided, this malignancy was found to have 100% affinity for skin, a short course, and poor prognosis. (J Am Acad Dermatol 2001;44:231-8.)