In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the lectin Ulex europaeus agglutinin I and the vessels in five fields counted within an ocular grid (area 7.84 x 10(-2) mm2) at 400 x magnification. CMMs (mean 0.48 mm) with regression had greater microvessel counts (27.2 +/- 5.1) compared with CMMs (mean 0.61 mm) without regression (mean 20.1 +/- 7.9) (P < 0.01). However, of particular interest, CMMs in the radial growth phase only and associated with regression (mean 0.40 mm) had strikingly greater vascularity (mean 28.7 +/- 6.9) versus radial growth phase CMMs (mean 0.44 mm) lacking regression (mean 16.4 +/- 6.6) (P = 0.0013). CMMs in the vertical growth phase (mean 0.81 mm) without regression had slightly less vascularity (mean 24.4 +/- 7.3) compared with vertical growth phase CMMs with regression (mean microvessels 27.2 +/- 5.1) (P = 0.1878) but significantly greater microvessels versus radial growth phase CMMs without regression (P = 0.0213). These results suggest that the onset of angiogenesis in thin CMMs is related to at least two phenomena: 1) inflammatory regression and 2) development of the vertical growth phase.