Full-thickness scalp defects with exposed calvarium pose a reconstructive challenge, particularly in patients with extensive comorbidities. A single-stage acellular dermal matrix and split-thickness skin graft reconstruction represents a simple and valuable surgical approach to achieving durable scalp coverage without requiring a donor-site or prolonged treatment. Reconstruction of full-thickness scalp defects with exposed calvarium is a difficult problem that generally requires local or free flap reconstruction. However, patients with significant medical comorbidities present a further challenge given the risks of a major surgical procedure. Simple skin graft directly onto bone frequently fails and does not provide durable coverage, while combined artificial skin substitute and split-thickness skin graft approach involves a prolonged treatment period with multiple-staged procedures. Herein, we present a case of an 82-year-old female patient with complex medical comorbidities with a large scalp defect and calvarial exposure following Moh's surgery. She was successfully treated with a single-stage acellular dermal matrix and a STSG reconstruction. Her treatment period was effectively shortened, and she had an excellent clinical outcome.