Progress in Melanoma Histopathology and Diagnosis Adriano Piris, MD a, *, Martin C. Mihm, Jr, MD b In this article, we discuss the recent developments in the histopathological interpreta- tion of primary malignant melanoma, including the evolving significance of prognostic factors. Although great strides have been made in the fields of immunohistochemistry and molecular biology, most of the criteria used in diagnosis and prognostication of melanoma derive from a thorough histopathological evaluation of the primary lesion. The greatest advances in the field of melanoma morphology started approximately 40 years ago when Clark and colleagues, McGovern, and Breslow independently made major contributions in the understanding of these lesions. 1–5 Clark and McGov- ern, almost simultaneously, described the different subtypes of melanoma and estab- lished prognostic parameters, whereas Breslow described a method to measure these lesions under the microscope. Since then, the cornerstone of the histopathological evaluation of malignant melanoma relies on the pattern of growth, microscopic levels of invasion, and thickness of the lesion. These concepts revolutionized the under- standing of this neoplasm that until then was considered a death sentence to the patient with only palliative excision as treatment option, which consisted almost always of radical mutilating surgery. Following these milestones in melanoma diagnosis, several elements of the primary tumor were described and correlated to prognosis, finessing even more the manage- ment of patients with malignant melanoma. 6–10 The conjunction of these morpholog- ical elements that have prognostic significance represents the ‘‘prognostic factors’’ currently used to guide management, and some of them are key elements of the Amer- ican Joint Committee on Cancer (AJCC) staging system. 11 a Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 820, Boston, MA 02114, USA b Department of Pathology and Dermatopathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Warren 820, Boston, MA 02114, USA * Corresponding author. E-mail address: apiris@partners.org (A. Piris). KEYWORDS  Melanoma  Histopathology  Borderline lesions  Prognosis  Dermal mitoses Hematol Oncol Clin N Am 23 (2009) 467–480 doi:10.1016/j.hoc.2009.03.012 hemonc.theclinics.com 0889-8588/09/$ – see front matter ª 2009 Elsevier Inc. All rights reserved.