Histiocytosis is a rare systemic disease, with heterogeneous and diverse clinical and radiological presentations. Diagnosis can therefore be intriguing. Several consensus recommendations have emerged in recent years, particularly with the advent of targeted therapies, changing the management and prognosis. The authors present two cases of neurohistiocytosis. The case of Langerhans cell histiocytosis was about an adolescent with polyuria-polydipsic syndrome in whom a cerebellar biopsy was inconclusive. The patient was lost to follow-up for one year and then returned with a multisystemic neurological, bone, and dermatological presentation. The diagnosis was confirmed based on skin biopsy results. The patients condition rapidly deteriorated after chemotherapy with vinblastine and corticosteroids, leading to his death. The case of Erdheim-Chester disease was about a 53-year-old man who presented with cerebellar syndrome. His biological and radiological workup showed neurological, endocrine (diabetes insipidus) renal (hairy kidney), and bone (fibrosis) involvement. The diagnosis was confirmed by femoral biopsy and the patient was treated with Cladribine with an excellent evolution with an 18-month follow-up. This manuscript aims to report our personal experience and underline the entitys heterogeneity, non-specificity, and repercussions.