Background/Objectives: Melanoma is a malignant tumour of melanocytes. Cutaneous melanoma accounts for the vast majority of cases and has benefitted from advances in targeted and immune checkpoint inhibitor therapies, leading to substantial improvements in survival. In contrast, mucosal and vulvovaginal melanomas are rare, aggressive subtypes with distinct molecular and immune profiles and poor prognoses. This review synthesises evidence comparing cutaneous, mucosal, and vulvovaginal melanoma, with emphasis on biology, treatment, and outcomes Methods: A narrative comparative review was undertaken, examining the published literature on the epidemiology, molecular and immune characteristics, and treatment outcomes of cutaneous, mucosal, and vulvovaginal melanoma, including systemic therapies and surgical approaches. Results: Cutaneous melanoma demonstrates high tumour mutational burden and frequent BRAF and NRAS mutations, underpinning the success of targeted therapy and immunotherapy. Mucosal and vulvovaginal melanomas exhibit lower mutational burden, distinct mutation patterns, and reduced immunogenicity, correlating with poorer treatment responses. Surgery remains the mainstay of management, though optimal margins in vulvovaginal melanoma are unclear. Recurrence rates are high, and five-year survival remains poor. Evidence for systemic therapy is limited to small retrospective cohorts and subgroup analyses, showing lower response and survival rates compared with cutaneous melanoma. Chemotherapy has minimal benefit. Conclusions: Mucosal and vulvovaginal melanomas are biologically and clinically distinct from cutaneous melanoma and continue to have poor survival outcomes. Their rarity restricts high-quality evidence, highlighting the need for collaborative, innovative research to inform effective treatment strategies.

Background: Intraoperative ultrasound (IOUS) is revolutionizing gynecologic oncology surgery by overcoming the limitations of traditional imaging and intraoperative assessment. Its real-time, high-resolution capabilities address critical needs in tumor localization, fertility preservation, refined intraoperative decisions, and complete cytoreduction. Methods: We reviewed clinical studies (1998–2024) evaluating IOUS applications, analyzing data on detection accuracy, surgical outcomes, and implementation challenges from peer-reviewed literature and institutional experiences. Results: IOUS demonstrates 88–93% sensitivity for subcentimeter metastases, refining surgical decisions in 25–40% of cases. Key outcomes include increased complete resection rates (68% to 87%), a 38% reduction in unnecessary lymphadenectomies, and successful fertility preservation in 92% of cases. Limitations include learning curves, 12% false-negative rate for micrometastases, and significant capital investment cost barriers. Conclusions: IOUS represents a transformative advance in precision surgery, improving both oncologic outcomes and quality of life. While standardization and accessibility challenges remain, ongoing technological innovations promise to solidify its role as a surgical standard.