We retrospectively reviewed 104 biopsy specimens of previously untreated skin acute graft-versus-host disease (GVHD) within 100 days after allogeneic stem cell transplantation, and analyzed the relationship between types of infiltrating cells and clinical outcomes. Counting the total number of CD8⁺ T cells, CD163⁺ macrophages, and CD1a⁺ dendritic cells in 4 fields under original magnification ×200, the infiltration of more than 200 cells of CD163⁺ macrophages (many macrophages [MM]) was the only significant predictor for refractory GHVD (odds ratio, 3.79; 95% confidence interval, 1.22-11.8; P = .02). In 46 patients given steroid treatments, MM was the only significant predictor for refractory acute GVHD (odds ratio, 5.05; 95% confidence interval, 1.19-21.3; P = .03). Overall survival of patients with MM was significantly lower than that of those with an infiltration of less than 200 cells of CD163⁺ macrophages. Macrophage infiltration of skin lesions could be a significant predictive factor for refractory GVHD and a poor prognosis.