The aim of this study was to develop a free flap of the male prepuce. First, a dissection feasibility study was performed in eight male cadavers. Dissection proved feasible, and the mean surface area of the prepuce, when folded out, was 46.7 cm2. The mean pedicle length was 15 cm, with a mean diameter of the inferior external pudendal artery at its origin of 1.2 mm and a mean diameter of the inferior external pudendal vein at its origin of 1.9 mm. Next, a viability study was performed by isolating a prepuce free flap during male-to-female sex reassignment procedures. The flap as well as the residual skin of the penis shaft remained well perfused. Thereafter, the new prepuce free flap was successfully applied for the reconstruction of defects of the floor of the mouth, tongue, and oropharynx in two patients. The thinness and pliability of the flap, its large surface area, the long vascular pedicle, and the limited donor-site morbidity are the major advantages of this new flap. The possibility to raise the flap simultaneously with the tumor resection is an additional advantage. The small caliber of the flap artery seems to be the only drawback.