Dermatopathology covers a large variety of entities, some having very similar histologic appearances. Immunohistochemistry is an important helpful tool that is useful in diagnosis, differential diagnosis as well as prognosis of a large series of cutaneous neoplasms. Immunohistochemistry is also an invaluable tool for assessing the tissue of origin or direction of differentiation of neoplastic cells. In some cases, this can result in a more precise diagnosis of the skin diseases and in a more adequate treatment for the patient. This presentation will focus in the role of some recently described immunohistochemical markers in order to decide the best therapeutic option. Speciﬁ cally, we will critically review the following markers in the following situations:
1. Immunohistochemical markers that demonstrate the presence of infectious microorganisms in cutaneous biopsies (VHS1, VHS2, CMV, VVZ, VEB, HHV8, Polyomavirus associated to Merkel tumor, parvovirus B19, anti-Treponema pallidum antibody, anti-Chlamydias antibody, anti-Leishmanias antibody, anti-BCG, etc).
2. Glut-1 and WT-1 in infantile hemangiomas and other vascular proliferations of the infancy.
3. The role of p63, podoplanin and EGFR in the differential diagnosis between primary cutaneous adnexal carcinomas and carcinomas metastatic to skin.
4. The lymphatic endothelial markers podoplanin, Lyve-1 and Prox-1 in order to distinguish classic angiosarcoma of the face from benign vascular proliferations, which may mimic angiosarcoma.
5. The c-Myc ampliﬁ cation in order to distinguish angiosarcoma secondary to radiotherapy from atypical but benign vascular proliferations in irradiated skin.
6. p16 and p21 in melanocytic neoplasms.
7. Immunohistochemical markers for differential diagnosis between Spitz nevus and spitzoid melanoma.
8. VE-1 antibody in the investigation of V600E Braf mutation in primary cutaneous melanoma and its metastases.
9. Adipophilin expression for diagnosis of sebaceous neoplasms and the loss of expression of the DNA mismatch
repair proteins MSH-2, MLH-1, MSH-6 and PMS2 for the
diagnosis of Muir-Torre syndrome.
10.The follicular stem cell marker PHLDA-1 for differential
diagnosis between trichoblastoma and basal cell