Langerhans cell histiocytosis (LCH) is a rare disorder that primarily affects children. Considering the intricate clinical presentation of this disease, the identification of specific biomarkers associated with susceptibility to LCH is essential for timely diagnosis and risk stratification. In this study, we examined the skin specimens from pediatric patients with LCH using RNAscope, immunohistochemistry, and sequencing techniques. We observed a notable correlation between elevated CCR6 expression in pathological tissues and LCH risk classification. Therefore, CCR6 expression may serve as an independent predictor of risk in clinical cases of LCH. Furthermore, the frequency of BRAF V600E mutations correlated with risk stratification. We discovered new mutations-H119Y and R108Q-in MAP2K1 in specimens with BRAF V600E mutations. Moreover, CCR6-positive tumors may exhibit an enhanced recruitment of lymphocytes expressing high CCR7 levels.