Background: Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH. Methods: We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed. Results: BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p = .001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression. Conclusions: In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.