We report the first documented case of an atypical form of transient reactive papulotranslucent acrokeratoderma (TRPA) in a patient heterozygous for the ΔF508 CFTR(cystic fibrosis transmembrane conductance regulator) mutation. TRPA represents a condition that classically presents with translucent to white plaques that become evident after water exposure. An atypical form with persistent lesions has also been described. Our patient is a 16-year-old girl with small, white papules coalescing into pebbly plaques on the palms. This condition is exacerbated after 5–10 min of water exposure and is associated with discomfort. The skin biopsy showed expanded stratum corneum, orthohyperkeratosis and dilation of eccrine ducts consisting with TRPA. A cystic fibrosis carrier state, barrier function defect, hyperhidrosis and the intake of cyclooxygenase inhibitors may have been pathogenic factors in our patient.