Female urethrectomy could be performed for various benign and malignant diseases; the decision to perform segmental or total urethrectomy is based on the pathology and extent of the urethral lesion. Female primary urethral cancers (PUCs) are rare, and most of the published studies mainly focus on oncological and survival outcomes [13, 19, 27, 39]. The female urethra is about 4 cm long and is divided based on the cellular lining or its relation to the surrounding anatomical structures, mainly the urethral sphincters. Histologically, the proximal third is lined by urothelial cells, and the distal two-thirds are lined by the squamous epithelium. The Skene (paraurethral) glands surround the urethra, and their ducts open near the external meatus. Anatomically, the female urethra is divided into the distal one-third (anterior segment) and the proximal two-thirds (posterior segment). The former can be resected without affecting the urinary sphincter. In all, 28%–45% of female primary urethral cancers (PUCs) are urothelial carcinomas and arise from the proximal urethra. Squamous cell carcinoma arises from the distal urethra and accounts for 19%–29% of female PUCs. Adenocarcinoma arises from the Skene glands, which are located alongside the entire urethra, and represents 28%–38% of female PUCs [9, 39] (Fig. 10.1).