Background: Distinction of rosacea and cutaneous lupus erythematosus (LE) can be challenging because of significant clinical and histologic overlap. A controlled study comparing these conditions is lacking. Objective: We compared the histologic features, T-cell subsets, and plasmacytoid dendritic cells in rosacea and LE. Methods: Biopsy specimens of rosacea (n = 27) and facial LE (n = 30) were retrospectively reviewed and reacted with Alcian blue and periodic acide-Schiff stains, and CD4, CD8, CD25, and CD123 immunostains. Results: LE demonstrates a lower CD4: CD8 ratio (1.74 vs 2.80, P =.0064), fewer CD4(+)CD25(+) regulatory T cells (13% vs 31%, P < .0001), and more CD123(+) plasmacytoid dendritic cells (18% vs 6%, P = .0137) than rosacea. The plasmacytoid dendritic cells in LE are more likely to form clusters (P = .0137) and comprise at least 20% of the infiltrate (P = .0340). Also associated with LE are follicular plugging (P = .0039), perineural lymphocytic infiltrate (P = .0211), abundant mucin deposition (P = .0031), and conspicuous basement membrane thickening (P = .0073), whereas Demodex infestation (P = .0064) and sebaceous hyperplasia (P = .0029) are significantly associated with rosacea. Limitations: Although statistically significant, the immunophenotypic differences are rather small and limited for routine use. Conclusion: The infiltrates in rosacea and LE differ immunophenotypically, and may aid in their distinction in addition to conventional histologic examination.