We report for the first time the fabrication of a three-dimensional tissue structure containing, in a continuous layer, the morphological features of a lip: epidermal skin, vermillion, and oral mucosa. This tissue engineered muco-cutaneous (M/C) equivalent was manufactured using human oral and skin keratinocytes grown on an acellular, nonimmunogenic dermal equivalent (AlloDerm(®)) to produce a tissue equivalent with similar anatomic and handling properties as native human lips. Confirmation of the structural composition of the construct was performed using routine histology and immunohistochemistry by identification of epithelial markers that are differentially expressed in separate anatomic areas of the lips. These full-thickness human lip skin equivalents can be used in surgical lip reconstruction in individuals suffering from lip loss from cancer, congenital deformations, and injuries after accidents. We propose this technique can be used as a general basis for tissue engineering of M/C junctions in other parts of the body, such as anus and vagina.