Background:Aquagenic keratoderma is a rare transient disease that occurs after water immersion and disappears shortly after drying. Most cases involve the palms and fingers bilaterally but it can also affect the soles. Few cases have been associated with drugs but its pathogenesis remains unclear.Main observation:We report a 60-year-old man with a 30-year-history of aquagenic keratoderma of the right palm without associated hyperhidrosis or history of drug intake. After unsuccessful treatment with 15% aluminium chloride hexahydrate gel, botulinum toxin A injections led to significant improvement within 2 weeks.Conclusions:To our knowledge, this case is the first report of idiopathic unilateral aquagenic keratoderma in the medical literature. It is the third report of successful treatment with botulinum toxin A which is in favor of a role of sweat glands in the pathogenesis of aquagenic keratoderma.