Ertekin SS, Podlipnik S, Ribero S, et al. - In this retrospective cohort study, researchers evaluated the performance of S100B in identifying early disease progression in high-risk melanoma individuals. The sample consisted of patients with an initial diagnosis of stage IIB, IIC, and III melanoma between January 2003 and July 2013. In total, 289 patients were followed up for 44 months (IQR 17–73) and metastases were developed by 45%. The classic method had 35.7% and 92.5% S100B protein sensitivity and specificity, respectively. In addition, the new method was implemented for patients who relapsed with normal S100B values and showed a sensitivity and specificity of 41.1% and 92.4%, respectively, enabling the identification of additional relapses that were absent by the classic method. Rising serum S100B values within the normal range can be an essential clue to disease progression during the follow-up of high-risk melanoma patients.