Background/Objectives: Keratinocyte carcinomas (KCs), including squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs), are the most common malignancies worldwide. Accurate delineation of surgical margins is essential to ensure oncological control while preserving favourable aesthetic outcomes. Optical coherence tomography (OCT) is a non-invasive, real-time, high-resolution technique that may facilitate preoperative and intraoperative margin assessment. This systematic review aims to analyse existing evidence on the use of in vivo OCT in the assessment of surgical margins in KC. Methods: This systematic review was conducted in accordance with the PRISMA guidelines. The articles included were retrieved from the PubMed, Web of Science, Scopus and EBSCO databases. The search was limited to studies published between 2010 and November 2025. The inclusion criteria were the application of in vivo OCT as an adjunctive method in the surgical excision of KC. A total of 11 studies involving 303 patients met the inclusion criteria. OCT was used preoperatively, intraoperatively, combined pre- and intraoperatively and both pre-, intra- and postoperatively, with most studies focused on margin delineation by itself. Results: Agreement between OCT and histopathology ranges from 84% to 95.5%. Surgical benefits were observed in both conventional surgery and Mohs micrographic surgery, including reduction in MMS stages (1.89 to 1.23), fewer stages required, and narrower excision margins. Conclusions: Based on data analysis, it may be assumed that in vivo OCT may have potential in non-invasive margin assessment in the surgical treatment of KC. The available evidence is limited by the heterogeneity of protocols and devices and variability between lesion types, as well as the small sample sizes and limited comparability. Further research should focus on randomised multicentre trials involving large cohorts, cost–benefit analysis and evaluation of operator-dependent variability.

Background: Keratinocyte carcinomas (KCs), including basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), are the most prevalent malignancies globally, particularly affecting sun-exposed facial areas. Achieving clear surgical margins in these regions is essential to ensure oncologic control while preserving cosmetic outcomes. Reflectance confocal microscopy (RCM) is a noninvasive imaging technique that enables real-time, high-resolution visualization of skin structures and may aid in margin assessment during KC surgery. This systematic review aims to evaluate the role of in vivo RCM in the surgical treatment of KCs. Methods: This review followed PRISMA guidelines. A comprehensive search of PubMed, Scopus, Web of Science, Medline, and EBSCO databases was conducted for studies published between January 1992 and December 2024. Inclusion criteria focused on clinical studies utilizing in vivo RCM for diagnostic or surgical applications in KC management. Results: Eighteen studies involving 1112 patients were included. RCM was used preoperatively in 5 studies and intraoperatively in another 5. Nine studies assessed margin delineation, while eight focused on diagnostic accuracy. RCM improved diagnostic confidence and allowed for more precise margin assessment, potentially reducing the extent of surgical excision in cosmetically sensitive areas. However, its broader clinical adoption is limited by operator dependency, procedural complexity, and lack of standardization. Conclusions: RCM shows promise as a supportive tool in KC surgery, particularly for preoperative planning. While its diagnostic utility is well established, its intraoperative role requires further validation. Larger, standardized, and cost-effective studies are needed to confirm its impact on surgical outcomes and patient quality of life.