To understand the role of the lateral thigh flap in head and neck reconstruction, we performed injection studies and anatomic dissections in 2 fresh and 61 preserved cadaver extremities followed by 10 clinical cases involving defects after tumor ablation. The flap, based on the third perforator of the profunda femoris artery, is designed on the posterolateral aspect of the distal thigh. The pedicle courses through the biceps short head, allowing optional transfer of this muscle. Defects of the oral cavity, pharynx, cervical esophagus, and external skin were successfully restored. One flap was unsuccessful because of intraoperative injury to the vascular pedicle. Compared with the radial forearm flap, the lateral thigh flap provides more tissue and the donor scar is more easily hidden, but the vascular pedicle is shorter, of smaller caliber, and more variable. The lateral thigh flap provides thin, pliable, and reliable tissue for a variety of needs in properly selected patients.