Background: In a recent prospective, multicenter, two-arm randomized controlled trial (RCT), we demonstrated that adjunctive reflectance confocal microscopy (RCM) in routine clinical practice provides clinical benefits, including safe melanoma detection and a 43.3% reduction in the number needed to excise (NNE). Methods: A cost–benefit analysis was conducted based on NNEs for standard care (5.3) and adjunctive RCM (3.0). Cost data were supplied by one center, applying a micro-costing approach from the hospital’s perspective. Costs were calculated for dermatology exams, excisions, medications, histopathology, and follow-up. The outcomes were extrapolated to provincial and national settings to assess the economic benefits of RCM. Results: The cost per patient for standard care was € 143.63, compared to € 114.74 for adjunctive RCM. The cost per melanoma excised with standard care (NNE 5.3) was € 904.87, almost twice the cost for RCM (€ 458.96). Annual regional and national costs for standard care were € 864,150.85 and € 11,491,849.00, respectively, while RCM reduced these to € 438,306.80 and € 5,828,792.00. Estimated annual savings with adjunctive RCM were € 425,844.05 regionally and € 5,663,057.00 nationally. The cost–benefit ratio for RCM was 3.89, meaning that for every € 1 spent on RCM, there is a benefit of € 3.89. Conclusion: In real-world clinical practice, adjunctive RCM offers significant economic advantages at local, regional, and national levels while maintaining patient safety and reducing unnecessary surgical procedures.