Background Acanthosis nigricans (AN) is a common dermatosis that presents with hyperpigmented, velvety thick plaques over intertriginous areas. Though a number of treatment modalities including chemical peels have been used, none provide long‐term and sustained improvement. Aim and objectives Our study evaluated the efficacy and safety of regular sessions of salicylic acid‐mandelic acid peeling over axillary AN lesions, which was followed by daily application of a topical combination of glycolic acid, urea, and cetylated fat esters for maintenance of effect for 9 months. Methodology A retrospective pilot study was conducted in Indian patients (Fitzpatrick skin type 4 or 5), aged 18–50 with benign hereditary AN involving the underarms, with or without affection of other typical sites. Data were retrieved of seventeen patients with AN involving the axillae. Patients were started on combination salicylic‐mandelic acid peel given every 2 weeks for a total of 6 sessions. Maintenance was done by night application of combination cream of glycolic acid, urea, and cetylated fat esters, which was continued for 9 months after completion of peeling sessions. Lesions were evaluated every 3 months of 9 months for improvement in pigmentation and skin thickening. Results All the patients (100%) showed significant improvement in both pigmentation and thickening of lesions. In terms of improvement in skin thickening, very good improvement was seen in 41%, while 29% patients had moderate improvement. In terms of improvement in pigmentation, 35% each had very good and moderate improvement. Post peel erythema (100%) and burning sensation (90%) were the most common encountered adverse effects which lasted for only 1–2 days. Patients were followed up for another 9 months during which no relapses were seen. Conclusion Combination of keratolytic chemical peels and topical mild keratolytic application ensures better therapeutic outcome in patients of AN with long lasting effect.

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