Hereditary palmoplantar keratoderma (PPK) is a rare inherited disorder characterized by marked hyperkeratosis of the palms and soles. Resultant painful fissuring severely limits mobility, and despite substantial advances in determining PPK genetic defects, therapeutic options remain limited. Case reports of patients with Olmsted syndrome (TRPV3 variation) treated with systemic erlotinib, an epidermal growth factor (EGF) receptor inhibitor, demonstrated improvement in their PPK.1,2 Given its adverse effect profile,3 clinicians may be hesitant about administering erlotinib systemically for PPK alone. With knowledge that EGF signaling regulates the expression of keratin 16,4,5 we report our experience of treatment with topical erlotinib for 2 patients (mother and son) with hereditary PPK due to a pathogenic keratin 16 variation (c.379C>T, p.[Arg127Cys]).