Melanoma has a wide spectrum of histologic features which mimic epithelial, hematologic, mesenchymal, and neural tumors. Immunohistochemistry has been the primary tool to distinguish melanomas from these other tumors; it has also been studied for use as an adjunct to distinguish benign and malignant melanocytic tumors and to elucidate prognosis. Furthermore, there has been extensive effort to find a suitable marker to differentiate spindle cell and desmoplastic melanoma from other tumors. We have reviewed the literature investigating melanocytic differentiation markers, proliferation markers, immunomodulatory markers, signaling molecules, and nerve growth factors and receptors. Despite the proliferation of immunohistochemical markers, S‐100 remains the most sensitive marker for melanocytic lesions, while markers such as HMB‐45, MART‐1/Melan‐A, tyrosinase, and MITF demonstrate relatively good specificity but not as good sensitivity as S‐100. No marker has proven useful in distinguishing spindle cell and desmoplastic melanomas from other tumors. Ki67 remains the most useful adjunct in distinguishing benign from malignant melanocytic tumors. None of the markers reviewed has been shown conclusively to have prognostic value for melanocytic neoplasms.

The Society for Hematopathology and European Association for Haematopathology workshop, from October 27 to 29, 2011, in Los Angeles, CA, exhibited many exemplary skin biopsy specimens with interesting inflammatory changes mimicking features of cutaneous lymphoma. This article reviews features observed in cutaneous lymphoid hyperplasia, cutaneous drug reactions, lupus-associated panniculitis, pityriasis lichenoides, hypereosinophilic syndrome, histiocytic necrotizing lymphadenitis, traumatic ulcerative granuloma with stromal eosinophils, and pigmented purpuric dermatosis, as well as a brief review of the pertinent literature and discussion of submitted conference cases. For the pathologist, it is important to be aware of diagnostic pitfalls as well as the limitations of ancillary testing (eg, clonality studies). Finally, correlation with total clinical information, good communication with clinical colleagues, close clinical follow-up with rebiopsy, and prudent use of laboratory studies are vital and will likely offer the best path toward a correct diagnosis.

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The authors have indicated no significant interest with commercial supporters.