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To delineate the anatomic architecture of the melolabial fold with surrounding structures and to elucidate potential implications for face-lift techniques.A total of 100 facial halves (from 50 cadaveric heads) were studied, including gross and microscopic dissection and histologic findings. Laboratory findings were correlated with intraoperative findings in more than 150 deep-plane face-lift dissections (300 facial halves) performed during the study period.In contrast to previous reports, the superficial musculoaponeurotic system (SMAS) was not found to form an investing layer in the midface. The SMAS, zygomatici muscles, and levator labii superioris alaeque nasi were found to be located in corresponding anatomic layers and to form a functional unit. Additional findings of the present study include the description of 3 structurally different portions of the melolabial fold, of an anatomic space below the levator labii superioris alaeque nasi (sublevator space), and of extensions of the buccal fat pad into the sublevator space and the middle third of the melolabial fold.The findings of the present study may contribute to augment our understanding of the complex anatomy of the midface and melolabial fold. Potential implications for modern face-lift techniques are discussed.