There have been 4 reported cases of squamous cell carcinoma (SCC) of the neovagina in transgender women. In this report, we present another case of neovaginal SCC in a transgender woman, which was HPV-related, with lung metastasis as the initial presentation, and which was also complicated by her previous history of metastatic renal cell carcinoma. This unique case highlights the diagnostic challenges in these unusual scenarios. Through this report, we hope to address the benefits of multidisciplinary tumor board rounds, provision of detailed clinical information, and familiarization of the transgender anatomy within the pelvis in this group of patients. We also propose that transgender women undergo a continuous annual follow-up after postoperative follow-up is completed. mation surgery, vaginoplasty is usually done by penile and scrotal skin inversion [3]. There have been 4 cases of SCC of the neovagina in transgender women reported, all presented as neovaginal discharge or bleeding [4][5][6][7]. In this report, we present another case of neovaginal SCC in a transgender woman, with lung metastasis as the initial presentation. This case had also been further complicated by her previous history of metastatic renal cell carcinoma.