Psoriatic onycho-pachydermo periostitis (POPP) is recognized as a rare subset of psoriatic arthritis, characterized by psoriatic onychodystrophy, connective tissue thickening above the distal phalanx, and a periosteal reaction. Therapy for this rare disease is based on treatments used for psoriatic arthritis, but traditional disease-modifying antirheumatic drugs, such as sulfasalazine and methotrexate, have shown inconsistent and unsatisfactory results. We report herein a successful therapeutic approach for POPP using the fully human anti–tumor necrosis factor (TNF) antibody adalimumab in a 42-year-old male patient. After 4 months of anti-TNF treatment, a remarkable normalization of the clinical appearance was achieved and magnetic resonance imaging showed complete resolution of the initial inflammatory lesions. Therefore, we consider a TNF-blocking strategy as promising for treatment of POPP.