An uncommon form of ichthyosiform erythroderma, Netherton Syndrome (NS) is inherited by an autosomal recessive pattern. Owing to eczematous skin lesions and the clinical features of atopy, NS is often initially diagnosed as atopic dermatitis. There are very few reports on NS in India. Hardly any case report or series that presents the use of biologicals for the treatment of NS reports the use of tofacitinib therapy. Therefore, it is essential to document such cases to promote further research to understand the underlying pathophysiology and find more effective treatments for the disease.A three-year-old boy, the second issue of a non-consanguineous marriage reported a history of waxing and waning of generalized reddish-brown scaly plaques all over the body and recurrent infections since birth. Multiple annular erythematous, partially blanchable papules to plaques with double-edge scaling were observed most prominently on the trunk. There was a diagnostic dilemma among erythrokeratoderma variabilis (EKV), atopic dermatitis (AD), and ichthyosis linearis circumflexa (ILC).The patient was administered betamethasone orally. However, there was no satisfactory relief or remission; therefore, oral tofacitinib therapy was initiated. The patient showed a good therapeutic response to oral tofacitinib at the dose of 0.3 mg/kg/day at the eighth-week follow-up.