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Halo reactions to melanocytic nevi are a well-recognized phenomenon. In contrast, halo reactions to Spitz's nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitz's nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem. We describe 17 examples of Spitz's nevus with halo reaction, and compare their immunohistochemical features with those of “ordinary” halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow-up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6-year follow-up period. Junctional, compound, intradermal, and combined types of Spitz's nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitz's nevi constituted more than one-half of examples in this series (9/17 cases). The combined Spitz's nevus included a combination of Spitz's nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitz's nevi, the lymphocytic response was often directed exclusively to the Spitz's nevic component. Important distinguishing features from malignant melanoma arising in a pre-existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile-appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitz's nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent. There were no obvious differences in immunohistochemical staining patterns among 4 Spitz's nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB-45, OPD4, CDS, TIA-1, CD1a, CD68, and Ki-67.