Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.

Most histiocytomas will regress within two or three months. Surgical removal may be necessary if the tumor does not regress or if it is growing rapidly to a large size. Histiocytomas should never be treated with an intralesional injection of a corticosteroid, as remission relies on recognition of the tumour by the body's immune system which is suppressed by steroids.

Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis has been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gys for children, 24-30 Gys for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.

The basis of management is to find and correct the underlying cause. Many times cats with EGC will respond to treatment with corticosteroids or to ciclosporin.

Excellent for single-focus disease. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.

Some patients have no symptoms, spontaneous remission, or a relapsing/remitting course, making it difficult to decide whether therapy is needed. In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible."

Therapeutic options include surgery, radiation therapy, and chemotherapy. Surgery is used to remove single lymph nodes, central nervous system lesions, or localized cutaneous disease. In 2014, Dalia and colleagues wrote that for patients with extensive or systemic Rosai–Dorfman disease, "a standard of care has not been established" concerning radiotherapy and chemotherapy.

Current treatment options include:

- Surgical debulking

- High-dose Corticosteroid therapy

- Cyclosporin

- Interferon-α

- Chemotherapy

- Vemurafenib. It would appear that approximately half these patients harbor point mutations of the BRAF gene at codon 600 substituting the amino acid glutamine for valine. Vemurafenib, an oral FDA approved targeted agent to the BRAF protein for melanoma, shows dramatic activity in patients Erdheim–Chester disease whose tumor contains the same mutation. In 2017 the US FDA approved vemurafenib for this indication.

- Radiation therapy

All current treatments have had varying degrees of success.

The vinca alkaloids and anthracyclines have been used most commonly in ECD treatment.

Malignant histiocytosis (also known as "Histiocytic medullary reticulosis") is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

Interdigitating dendritic cell sarcoma is a form of malignant histiocytosis affecting dendritic cells.

It can present in the spleen. It can also present in the duodenum.

Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis.

Langerhans cell sarcoma is a form of malignant histiocytosis. It should not be confused with Langerhans cell histiocytosis, which is cytologically benign. Langerhans cell sarcoma is known to transform into leukemia. It can present in the lung, but such cases are rare.

Langhans giant cells are named after Theodor Langhans (1839–1915), a German pathologist.

They should not be confused with Langerhans cells, which are mononuclear epidermal dendritic cells derived (like Langhans cells) from monocytes and named after Paul Langerhans. (The Islets of Langerhans are also named after Paul Langerhans.)

Although patients can receive intensive antibiotherapy and even granulocyte transfusions from healthy donors, the only current curative therapy is the hematopoietic stem cell transplant. However, progress has been made in gene therapy, an active area of research. Both foamyviral and lentiviral vectors expressing the human ITGB2 gene under the control of different promoters have been developed and have been tested so far in preclinical LAD-I models (such as CD18-deficient mice and canine leukocyte adhesion deficiency-affected dogs).

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

X-type histiocytoses are a clinically well-defined group of cutaneous syndromes characterized by infiltrates of Langerhans cells, as opposed to Non-X histiocytosis in which the infiltrates contain monocytes/macrophages. Conditions included in this group are:

Langerhans cells are dendritic cells (antigen-presenting immune cells) of the skin and mucosa, and contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as in the mucosa of the mouth, foreskin, and vagina. They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).

Non-X histiocytoses are a clinically well-defined group of cutaneous syndromes characterized by infiltrates of monocytes/macrophages, as opposed to X-type histiocytoses in which the infiltrates contain Langerhans cells. Conditions included in this group are:

A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning "tissue", and cyte, meaning "cell").

In pathology, dermatopathic lymphadenopathy, also dermatopathic lymphadenitis, is lymph node pathology due to skin disease.

Eosinophilic granuloma is a form of Langerhans cell histiocytosis. It is a condition of both human and veterinary pathology. Colloquially, the reaction pattern is sometimes referred to as a rodent ulcer.

Feline eosinophilic granuloma complex is synonymous with "feline eosinophilic skin diseases". This is considered to be a cutaneous reaction pattern that can be the manifestation of a number of underlying infections, allergies or ectoparasite infestations. It can also be idiopathic, that is have no known underlying trigger. The eosinophilic reaction is common in feline inflammatory disease and the eosinophilic granuloma can be a hereditary reaction pattern in some lines of domestic cats.

In medicine, histiocytosis refers to an excessive number of histiocytes, ("tissue macrophages"), and is typically used to refer to a group of rare diseases which share this as a characteristic. Occasionally and confusingly, the term "histiocytosis" is sometimes used to refer to individual diseases.

According to the Histiocytosis Association of America, 1 in 200,000 children in the United States are born with histiocytosis each year. HAA also states that most of the people diagnosed with histiocytosis are children under the age of 10, although the disease can afflict adults. The University of California, San Francisco, states that the disease usually occurs from birth to age 15.

Histiocytosis (and malignant histiocytosis) are both important in veterinary as well as human pathology.

Hand–Schüller–Christian disease is associated with multifocal Langerhans cell histiocytosis.

It is associated with a triad of exophthalmos, lytic bone lesions (often in the skull), and diabetes insipidus (from pituitary stalk infiltration).

It is named for the US-American pediatrician Alfred Hand Jr, the Austrian neurologist and radiologist Arthur Schüller, and the US-American internist Henry Asbury Christian, who described it in 1893, 1915/16 and 1919

Langerhans cells may be initial cellular targets in the sexual transmission of HIV, and may be a target, reservoir, and vector of dissemination.

Langerhans cells have been observed in foreskin, vaginal, and oral mucosa of humans; the lower concentrations in oral mucosa suggest that it is not a likely source of HIV infection relative to foreskin and vaginal mucosa.

On March 4, 2007 the online Nature Medicine magazine published the research letter "Langerin is a natural barrier to HIV-1 transmission by Langerhans cells." One of the authors of the study, Teunis Geijtenbeek, said that "Langerin is able to scavenge viruses from the surrounding environment, thereby preventing infection" and "since generally all tissues on the outside of our bodies have Langerhans cells, we think that the human body is equipped with an antiviral defense mechanism, destroying incoming viruses."

Surgery may be difficult due to the location of these tumors. Surgery alone often leads to recurrence. Chemotherapy is very effective for TVTs. The prognosis for complete remission with chemotherapy is excellent. The most common chemotherapy agents used are vincristine, vinblastine, and doxorubicin. Radiotherapy may be required if chemotherapy does not work.

Letterer–Siwe disease is one of the four recognized clinical syndromes of Langerhans cell histiocytosis (LCH). It causes approximately 10% of LCH disease and is the most severe form. Prevalence is estimated at 1:500,000 and the disease almost exclusively occurs in children less than three years old. The name is derived from the names of Erich Letterer and Sture Siwe.