The 2018 WHO edition on the classification of cutaneous melanocytic tumors recognizes eight evolutionary pathways of melanoma and describes tumors of uncertain malignant potential for each. When histology and immunohistochemistry do not support a confident conclusion about its malignant potential, a window of diagnostic uncertainty is created. Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are highly specific for melanoma and can be used as an ancillary technique to acquire a higher level of confidence in the diagnosis. However, little is known about the cost-effectiveness of testing for TERTp mutations. The aims of this study were to determine how often knowledge of the TERTp mutation status contributed to the final diagnosis and to develop a micro-costing framework to calculate cost-effectiveness. A retrospective analysis of all cutaneous melanocytic lesions that were discussed in the Noord-Nederland Melanoma Panel from January 2021 to October 2022 was performed to identify the cases in which the preliminary histopathological diagnosis was uncertain regarding malignancy (ambiguous, likely benign, or likely malignant). For cases in which a TERTp mutation analysis was performed, the final diagnoses were collected, and it was determined whether this impacted the overall conclusion. A micro-costing framework was established to model the financial impact of introducing TERTp mutation analyses and subsequent clinical procedures. The study included 367 cases, of which 175 diagnoses of uncertain malignant potential were initially reported. TERTp mutation analysis was performed for 151/175 (86%). In 38% of these cases, a higher level of confidence regarding malignant potential was obtained. The implementation of TERTp mutation analyses for cutaneous melanocytic proliferations with uncertain malignant potential can narrow the window of diagnostic uncertainty. For the patient group with an initial uncertain diagnosis, the increased cost for molecular testing (86.145 €) was compensated by a ...