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Large cranial defects (70 cm2 or more) of complex geometric shapes (bifrontal or involving supraorbital ridges) that are associated with significant cutaneous contracture or soft tissue loss are challenging to reconstruct. We have treated 10 patients with complex cranial defects through a staged approach. Reconstructing the defect involved several steps. Before each surgery, we constructed a craniofacial prosthesis from polymethyl methacrylate to fit the patient's individual defect. When indicated, adjacent skin was expanded with a subcutaneous tissue expander. Finally, we carried out a cranioplasty and placed the prosthesis. Operative closure of the defect was facilitated by microplate and screw fixation with minimal prothesis contouring. Secure, vital, nontension skin closure was performed with the delayed, expanded local flap. Exposure to free polymer and exothermic reaction was avoided. Cosmetic results in these patients with high-volume, geometrically complex defects were excellent. No complications occurred, and the overall operative time was shortened.