Palmoplantar keratoderma is a heterogeneous group of disorders affecting keratinization on the palms and soles of the feet. The benign lesions cause pain and limit function. Treatment of palmoplantar keratoderma remains problematic and restricted to symptomatic therapy; no cure exists. Medical treatments and surgical excision are currently the mainstay of therapy; however, these treatments have limited success, significant morbidity, and recurrence is common. We present a case report of successful treatment with CO2 laser therapy and a review of the literature.