The treatment for CGCG is thorough curettage. A referral is made to an oral surgeon. Recurrence ranges from 15%–20%. In aggressive tumors, three alternatives to surgery are undergoing investigation:

- corticosteroids;

- calcitonin (salmon calcitonin);

- interferon α-2a.

These therapeutic approaches provide positive possible alternatives for large lesions. The long term prognosis of giant-cell granulomas is good and metastases do not develop.

Excision of the entire lesion, with adequate margin, will remove the lesion, allow full tissue diagnosis, and leave a planned surgical wound which can usually be repaired with a good cosmetic result. However, removing the entire lesion (especially on the face) may present difficult problems of plastic reconstruction. (On the nose and face, Mohs surgery may allow for good margin control with minimal tissue removal, but many insurance companies require the definitive diagnosis of a malignancy "before" they are prepared to pay the extra costs of Mohs surgery.) Especially in more cosmetically-sensitive areas, and where the clinical diagnosis is reasonably certain, alternatives to surgery may include no treatment (awaiting spontaneous resolution).

On the trunk, arms, and legs, electrodesiccation and curettage often suffice to control keratoacanthomas until they regress. Other modalities of treatment include cryosurgery and radiotherapy; intralesional injection of methotrexate or of 5-fluorouracil have also been used.

Recurrence after electrodesiccation and curettage can occur; it can usually be identified and treated promptly with either further curettage or surgical excision.

Surgical excision is the standard of care. Some individuals advocate the use of hair removal laser for the treatment of congenital nevi. While this is likely safe and effective for small congenital nevus, laser removal for larger lesions might pose a liability for the laser surgeon if malignancy developed from a deep (dermal) component of the nevus that is not reached by the laser. Repigmentation after laser treatment of congenital nevi or superficial curettage supports this concern.

Many are surgically removed for aesthetics and relief of psychosocial burden, but larger ones are also excised for prevention of cancer, although the benefit is impossible to assess for any individual patient. Proliferative nodules are usually biopsied and are regularly but not systematically found to be benign. Estimates of transformation into melanoma vary from 2-42% in the literature, but are most commonly considered to be at the low end of that spectrum due to early observer bias.

The goal of treatment is to improve the appearance of lesions since they are otherwise not serious and typically do not cause symptoms. Many treatment methods have been attempted however, complete removal is uncommon. No single treatment method has been shown to consistently work. Both medical and surgical treatments have been studied, each with variable success. Common destructive treatment methods include carbon dioxide lasers, dermabrasion, surgical excision, electrocoagulation and chemical peels. Many of these methods are very time consuming and require multiple treatment sessions.Carbon dioxide lasers are the most commonly practiced method; however, can cause thermal damage leading to scarring in the area. Medical therapies include topical atropine, topical retinoids and oral tranilast.

The most common adverse side effects include redness, skin discoloration and pain. Other side effects include blistering and scarring.

Usually, treatment of a lipoma is not necessary, unless the tumor becomes painful or restricts movement. They are usually removed for cosmetic reasons, if they grow very large, or for histopathology to check that they are not a more dangerous type of tumor such as a liposarcoma. This last point can be important as the characteristics of a "bump" are not known until after it is removed and medically examined.

Lipomas are normally removed by simple excision. The removal can often be done under local anaesthetic, and takes less than 30 minutes. This cures the great majority of cases, with about 1–2% of lipomas recurring after excision. Liposuction is another option if the lipoma is soft and has a small connective tissue component. Liposuction typically results in less scarring; however, with large lipomas it may fail to remove the entire tumor, which can lead to regrowth.

New methods under development are supposed to remove the lipomas without scarring. One is removal by injecting compounds that trigger lipolysis, such as steroids or phosphatidylcholine.

Once a patient with neurocutaneous melanosis becomes symptomatic, little can be done to improve prognosis as there is no effective treatment for the disorder. Most therapies are designed to treat the symptoms associated with the disorder, mainly those related to hydrocephalus. A ventriculoperitoneal shunt to relieve intracranial pressure is the preferred method.

Chemotherapy and radiotherapy have been shown to be ineffective in cases of neurocutaneous melanosis where malignancy is present. Additionally, due to the total infiltration of the central nervous system by these lesions, surgical resection is not a viable treatment option.

It has been demonstrated that early embryonic, post-zygotic somatic mutations in the NRAS gene are implicated in the pathogenesis of NCM. Recently, experimental treatment with MEK162, a MEK inhibitor, has been tried in a patient with NCM and progressive symptomatic leptomeningeal melanocytosis. Pathological studies with immunohistochemical and Western Blot analyses using Ki67 and pERK antibodies showed a potential effect of MEK inhibiting therapy. Further studies are needed to determine whether MEK inhibitors can effectively target NRAS-mutated symptomatic NCM.

The cysts can be removed via , though conventional cyst excision techniques have proven impractical, and a specialized regimen is required.

Surgical excision is the preferred method of treatment for benign glomus tumors.

General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials. Surgery is the treatment of choice if the tumor is determined to be resectable. Curettage is a commonly used technique. The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery.

Patients with tumors that are not amenable to surgery are treated with radiation therapy. However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion. Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate, which are thought to induce apoptosis in the MNGC fraction, preventing tumor-induced osteolysis. Indeed, "in vitro" studies have shown zolidronate to be effective in killing osteoclast-like cells. More recently, humanized monoclonal antibodies such as Denosumab targeting the RANK ligand have been employed in treatment of GCTOB in a phase II study. This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis.

Desmoplastic trichoepithelioma is benign tumor and can be managed safely with surgical removal, electrodesiccation and curettage.

Since this lesion is usually a complication of long standing otitis media, it is important to use an appropriate antibiotic therapy regimen. If the patient fails first line antibiotics, then second-line therapies should be employed, especially after appropriate culture and sensitivity testing. Surgery may be required if there is extension into the mastoid bone, or if a concurrent cholesteatoma is identified during surgery or biopsy. In general, patients have an excellent outcome after appropriate therapy.

Large and especially giant congenital nevi are at higher risk for malignancy degeneration into melanoma. Because of the premalignant potential, it is an acceptable clinical practice to remove congenital nevi electively in all patients and relieve the nevocytic overload.

Outpatient treatments such as interventional radiology, lasers, and physical therapy are employed to reduce the severity of the vascular lesions. However, in some cases lasers have caused a reaction in the tissue causing it to expand and become exposed to infection. Excision and grafting may be necessary to remove the lesion. Recovery time on such an operation ranges from 3 to 12 weeks depending on location of the graft, healing time and the possibility of complications.

TSC typically affects multiple organ systems and manifests differently in each patient and in different stages of the life course. Drug therapy, surgery, and other interventions can be effective in managing some of the manifestations and symptoms of TSC.

In the United States, the Food and Drug Administration has approved several drugs for managing some of the major manifestations of TSC. The antiepileptic medication vigabatrin was approved in 2009 for treatment of infantile spasms and was recommended as first-line therapy for infantile spasms in children with TSC by the 2012 International TSC Consensus Conference. Adrenocorticotropic hormone was approved in 2010 to treat infantile spasms. Everolimus was approved for treatment of TSC-related tumors in the brain (subependymal giant cell astrocytoma) in 2010 and in the kidneys (renal angiomyolipoma) in 2012. Everolimus also showed evidence of effectiveness at treating epilepsy in some people with TSC. In 2017, the European Commission approved everolimus for treatment of refractory partial-onset seizures associated with TSC.

Neurosurgical intervention may reduce the severity and frequency of seizures in TSC patients. Embolization and other surgical interventions can be used to treat renal angiomyolipoma with acute hemorrhage. Surgical treatments for symptoms of lymphangioleiomyomatosis (LAM) in adult TSC patients include pleurodesis to prevent pneumothorax and lung transplantation in the case of irreversible lung failure.

Other treatments that have been used to treat TSC manifestations and symptoms include a ketogenic diet for intractable epilepsy and pulmonary rehabilitation for LAM.

Treatment usually involves surgical removal of the lesion down to the bone. If there are any adjacent teeth, they are cleaned thoroughly with scaling and root planing (SRP) to remove any possible source of irritation. Recurrence is around 10%.

Spiradenoma, also spiroma or eccrine spiradenoma, is a cutaneous condition that is typically characterized, clinically, as a solitary, deep-seated dermal nodule of approximately one centimeter, occurring on the ventral surface of the body. Spiradenoma lesions are benign sudoriferous tumors, and have also been described as cystic epitheliomas of the sweat glands.

The histological origin is controversial.

Most patients with thyroid adenoma can be managed by watchful waiting (without surgical excision) with regular monitoring. However, some patients still choose surgery after being fully informed of the risks. Regular monitoring mainly consists of watching for changes in nodule size and symptoms, and repeat ultrasonography or needle aspiration biopsy if the nodule grows.

A desmoplastic trichoepithelioma is a cutaneous condition characterized by a solitary, firm skin lesion on the face.

The majority of patients with neurocutaneous melanosis are asymptomatic and therefore have a good prognosis with few complications. Most are not diagnosed, so definitive data in not available. For symptomatic patients, the prognosis is far worse. In patients without the presence of melanoma, more than 50% die within 3 years of displaying symptoms. While those with malignancy have a mortality rate of 77% with most patients displaying symptoms before the age of 2.

The presence of a Dandy-Walker malformation along with neurocutaneous melanosis, as occurs in 10% of symptomatic patients, further deteriorates prognosis. The median survival time for these patients is 6.5 months after becoming symptomatic.

A giant solitary trichoepithelioma is a cutaneous condition characterized by a skin lesion that may be up to several centimeters in diameter.

Removal of the mast cell tumor through surgery is the treatment of choice. Antihistamines, such as diphenhydramine, are given prior to surgery to protect against the effects of histamine released from the tumor. Wide margins (two to three centimeters) are required because of the tendency for the tumor cells to be spread out around the tumor. If complete removal is not possible due to the size or location, additional treatment, such as radiation therapy or chemotherapy, may be necessary. Prednisone is often used to shrink the remaining tumor portion. H2 blockers, such as cimetidine, protect against stomach damage from histamine. Vinblastine and CCNU are common chemotherapy agents used to treat mast cell tumors.

Toceranib and masitinib, examples of receptor tyrosine kinase inhibitors, are used in the treatment of canine mast cell tumors. Both were recently approved by the U.S. Food and Drug Administration (FDA) as dog-specific anticancer drugs.

Grade I or II mast cell tumors that can be completely removed have a good prognosis. One study showed about 23 percent of incompletely removed grade II tumors recurred locally. Any mast cell tumor found in the gastrointestinal tract, paw, or on the muzzle has a guarded prognosis. Previous beliefs that tumors in the groin or perineum carried a worse prognosis have been discounted. Tumors that have spread to the lymph nodes or other parts of the body have a poor prognosis. Any dog showing symptoms of mastocytosis or with a grade III tumor has a poor prognosis. Dogs of the Boxer breed have a better than average prognosis because of the relatively benign behavior of their mast cell tumors. Multiple tumors that are treated similarly to solitary tumors do not seem to have a worse prognosis.

Mast cell tumors do not necessarily follow the histological prognosis. Further prognostic information can be provided by AgNOR stain of histological or cytological specimen. Even then, there is a risk of unpredictable behavior.

Generalized trichoepitheliomas are characterized histologically by replacement of the hair follicles by trichoepithelioma-like epithelial proliferations associated with hyperplastic sebaceous glands.

Isthmicoma (also known as "Infundibuloma," and "Tumor of the follicular infundibulum") are a cutaneous condition characterized by flat, keratotic papules of the head and neck, skin lesions that are usually solitary.

Eccrine angiomatous hamartoma usually appear as a solitary nodular lesion on the acral areas of the extremities, particularly the palms and soles.

Keratoacanthoma usually occurs in older individuals. As with squamous cell cancer, it seems likely that ultraviolet light from the sun causes the development of KA. As with squamous cell cancer, sporadic cases have been found co-infected with the human papilloma virus (HPV).

Many new treatments for Melanoma are also known to increase the rate of Keratoacanthoma, such as the B-Raf inhibitor drugs Vemurafenib and Dabrafenib.