Mixed histiocytoses are a rare and recently recognized subset of histiocytic disorders that may involve the skin, characterized by the synchronous or metachronous development of lesions with Langerhans and/or non‐Langerhans cell histiocytosis histopathological features. Around 10% of patients diagnosed with histiocytosis may develop a hematological malignancy, often with dramatic prognostic consequences. We hereby describe the exceptional case of a patient developing a MAP2K1‐driven mixed histiocytosis with Langerhans cell histiocytosis, Rosai‐Dorfman‐Destombes disease, and Erdheim‐Chester disease features and cutaneous involvement, progressing to a fatal and clonally‐related acute myeloid leukemia. We reviewed the literature on similar cases and discussed the histopathological difficulties in their diagnosis and their clinical‐pathological features.