Background Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. Objective We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. Methods In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8+ T lymphocytes, and E-cadherin. Results The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8+ T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). Limitation The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. Conclusion The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion. Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8+ T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8+ T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion.