BACKGROUND Activating mutations of the BRAF-gene provide an important treatment target in melanoma patients. However, prognostic role of several biochemical markers in relation to the mutation status is not clear yet. OBJECTIVES Prognostic significance of BRAF mutation in melanoma patients was analyzed and correlated to different additional markers. PATIENTS AND METHODS 162 melanoma stage IV patients with known BRAF-mutation status were included. Clinical, histopathological and laboratory information was collected and compared between BRAF-mutant (BRAFm) and wildtype (BRAFwt) melanoma patients at time of first distant metastasis. RESULTS 88 patients (54.3%) were BRAFm (V600E or K). At first distant metastasis S100B levels in BRAFm patients were more frequently elevated and significantly higher (p = 0.013 resp. p = 0.021). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared to patients with elevated S100B levels (p < 0.001). However, in BRAFm melanoma, elevated S100B levels showed no prognostic influence (p = 0.18). Elevated LDH levels had a significant negative impact on mOS in both BRAFm and BRAFwt groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared to BRAFm patients without BRAFi treatment (p = 0.012). However, no difference in mOS between BRAFm patients without BRAFi treatment and BRAFwt patients was observed. CONCLUSIONS The analysis confirms the better mOS in BRAFm patients treated with BRAFi. Interestingly, BRAFm patients not treated with BRAFi show similar survival curves as BRAFwt patients. Additionally, elevated LDH is a BRAF-independent prognostic parameter in all patients, whereas S100B has prognostic significance in BRAFwt patients only. This article is protected by copyright. All rights reserved.