Melanoma is a cancer with a high incidence rate that, despite the significant development of therapeutic options, still remains a major problem. The identification of biomarkers to select the right therapy for the right patient is one of the possibilities to improve the prognosis of patients. Potentially, the function of biomarkers could be played long non-coding RNAs (lncRNAs). The expression of selected 90 lncRNAs in serum from 30 metastatic melanoma patients with confirmed mutations in the BRAF V600 E or K gene was studied. Serum was collected prior to BRAF and MEK inhibitor therapy. The control group consisted of 16 healthy volunteers. A total of 41 lncRNAs were identified the expression of which differed statistically significantly between the patient group and the healthy volunteers. In addition, it was shown that the expression of HOXA3as (p = 0.033), PRINS (p = 0.036) and RNCR3 (p = 0.045) is higher in patients with the presence of CNS metastases, PFS inhibiting RNA (p = 0.048) is higher among patients with the presence of hepatic metastases, UCA1 (p = 0.008) expression is lower in patients with increased lactate dehydrogenase levels, while HOTAIRM1 (p = 0.044) and E2F4 antisense (p = 0.040) expression is lower in patients over 60 years of age. In addition, patients with high lincRNASFMBT2 expression showed longer median PFS (8.75 vs. 17.5 months, p = 0.0319) and OS (9.75 vs. 38 months (open observation, p = 0.0253). The obtained results require validation on a larger group of patients. If the results are confirmed, the indicated lncRNAs may play an important role as diagnostic and prognostic markers.