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Objectives: To evaluate the efficacy, safety, and clinical durability of Pinholxell Therapy, a novel dual-mode CO₂ laser method, for severe, refractory nevus comedonicus (NC), a dermatological disorder characterized by clusters of keratin-plugged dilated follicular openings significantly affecting patients ’s cosmetic appearance and psychological well-being. Methods: A 43-year-old female patient presented with extensive NC involving the right side of her face, spanning from the ear, across the cheek and mouth, and extending down to the neck. Initially deemed unsuitable for skin grafting, the patient underwent 55 sessions of Pinholxell Therapy over a 15-year period. This innovative method combines deep CO₂ laser-induced pinhole columns with fractional laser resurfacing, promoting simultaneous deep dermal remodeling and superficial epidermal regeneration. Results: Pinholxell Therapy yielded substantial clinical improvements, including nearly complete anatomical reduction of follicular openings, notable reductions in keratinous comedones, enhanced skin texture smoothness, and significantly improved overall cosmetic appearance. Additionally, these therapeutic outcomes contributed to substantial psychological benefits for the patient, demonstrating long-term efficacy and safety. Conclusions: Pinholxell Therapy is a promising, durable, and effective advanced therapeutic intervention for severe, refractory nevus comedonicus, providing both significant clinical improvement and notable enhancement of patient quality of life.