Background: Acanthosis nigricans (AN) is a common cutaneous condition that can be a manifestation of systemic disease. AN is characterized by hyperpigmented and hyperkeratotic velvety skin lesions that presents mainly on the flexural sites, for example, the neck, the axillae, and groin. Objective: The aim of this study was to evaluate the clinical efficacy of fractional carbon dioxide laser versus glycolic acid peel 70% in treatment of pseudo-acanthosis nigricans through assessing changes in degree of area index, severity and texture of lesion. Patients and methods: Twenty patients with pseudo-acanthosis nigricans were included in this study. They were chosen from the Outpatient Clinic of Dermatology, Andrology & STDs department, Mansoura University Hospitals. All cases were subjected to fractional CO₂ laser on the right side of the neck and glycolic acid peel 70% on the left side of the neck. Each patient was followed up for 3 and half months. Results: There was statistically significant difference regarding improvement in area index, severity and texture across time subjected to glycolic acid (GA) peeling 70%. There was statistically significant difference regarding improvement in area index, severity and texture across time subjected to fractional CO2 laser. There was no statistically significant difference when comparing effect of laser and peeling on adult and children. There was no statistically significant difference when comparing effect of laser and peeling on rural and urban cases. Conclusion: Acanthosis nigricans is a difficult dermatosis to treat, although there are many methods of treatment. Glycolic acid peeling 70% and fractional CO2 laser are considered effective modalities for AN treatment. However, GA peeling was more effective but statically insignificant.