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BACKGROUND. A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers. METHODS. Markers of angiogenesis that included expression of the vascular endothelial growth factor A (VEGF-A) and microvessel density counts (MVD) were evaluated in 13 prospectively collected benign nevi (BN) and 19 DN from 16 individuals and in a comparison group of 17 primary melanomas (16 archival samples and 1 prospective melanoma). RESULTS. VEGF expression in melanocytic cells (mean ± standard error [SE]) was low or absent in BN (3.4 ± 1.4), increased significantly in DN (41.0 ± 10.1; P = .0003 for BN vs DN), and increased further in primary melanoma (119.9 ± 28.3; P = .06 for DN vs melanoma). MVD using CD31 (mean ± SE [percentage × intensity]) followed a similar pattern with similarity between BN (2.6 ± 0.7; N = 13) and DN (2.2 ± 0.8; N = 19; P = .4 for BN vs DN), whereas primary melanomas were significantly higher (39.4 ± 6.4; N = 17; P = .0001 for BN or DN vs melanoma). CONCLUSIONS. In a prospective setting, the current data suggested that increased VEGF-A expression in DN may be a good indicator of preneoplastic change in melanocytic lesions with the potential for improving the understanding and prevention of the transformation of DN to melanoma. Cancer 2007. © 2007 American Cancer Society.