Both keloids (KLs) and hypertrophic scars (HSs) are considered as dermal fibroproliferative diseases that differ clinically and histopathologically. Although several factors have been postulated in the etiopathogenesis of these conditions, there has been growing evidence to suggest the role of COXs in the pathogenesis of abnormal wound healing because of the reduction of formation of KL and HS in patients using nonsteroidal anti-inflammatory drugs and a COX-2 inhibitor. The aim of the present work is to evaluate the pattern and localization of COX-1 and COX-2 expression in KL and HS compared with surgical scars. COX-1 and COX-2 were analyzed on skin biopsies of 30 patients who presented with KL (15) and HS (15) and 10 normal surgical scars (controls). Both COX-1 and COX-2 were expressed not only in dermal components (fibroblasts, inflammatory cells, and endothelial cells) but also in keratinocytes of the overlying epidermis in the different studied scar lesions. The percentage of COX-1 expression increased progressively from surgical scar (40%) to HS (53.3%) to KL (100%) with a statistically significant difference (P = 0.002). COX-2 was expressed in 100% of surgical scars, 73.3% of HS and 86.7% of KL with the absence of significant differences (P > 0.05). The significant difference in COX-1 expression between HS and KL may refer to the presence of different pathways for the emergence of these diseases. The expression of COX-2 in all scars (normal or abnormal) indicates its active role as an inflammatory mediator. Keratinocytes play an active role in induction of scarring by up-regulation of inflammatory mediators, such as COX-1 and COX-2.