Treatment depends upon the site and the extent of the disease. Clear cell sarcoma is usually treated with surgery in the first place in order to remove the tumor. The surgical procedure is then followed by radiation and sometimes chemotherapy. Few cases of clear cell sarcoma respond to chemotherapy. Several types of targeted therapy that may be of benefit to clear cell sarcoma patients are currently under investigation.

Radiotherapy is commonly used to treat Merkel-cell cancers. The radiotherapy fields used are usually very large so as to cover sufficient areas of skin. This is necessary because of MCC's aggressive local and regional metastatic behavior.

Adjuvant radiotherapy has been shown to be effective in reducing the rates of recurrence and in increasing the survival of patients with MCC. Patients who present with no distant metastases and a negative sentinel lymph node biopsy have a very good prognosis when treated with both surgery and radiotherapy (approximately 90% survival rate at five years).

Metastatic MCC may respond to treatment with chemotherapy and/or radiation, but current multimodal therapies are usually not curative. Intensive treatment can be effective in shrinking the tumor and improving operability when tumors are too large to be removed or located in a place where removal would be difficult or dangerous, or in palliation of signs and symptoms caused by metastatic tumors.

The U.S. Food and Drug Administration granted in March 2017 an accelerated approval to the checkpoint-inhibitor avelumab for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC). This is the first FDA-approved treatment for metastatic MCC. Avelumab targets the PD-1/PD-L1 pathway (proteins found on the body’s immune cells and some cancer cells). By blocking these interactions, avelumab may help the body’s immune system attack cancer cells.

Therapies for metastatic melanoma include the biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.

Epithelioid sarcoma (especially advanced stage, recurrent, or metastasized disease) has been shown to be resistant to traditional cancer therapies, necessitating further exploration of novel treatment methods and techniques. Because of the relatively poor response of epithelioid sarcoma to traditional cancer treatments (surgery, chemotherapy, and radiation), new treatment strategies are being looked to.

Various chemotherapy agents, including temozolomide, dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)), as well as local perfusion, are used by different centers. The overall success in metastatic melanoma is quite limited.

IL-2 (Proleukin) was the first new therapy approved (1990 Europe, 1992 USA) for the treatment of metastatic melanoma in 20 years. Studies have demonstrated that IL-2 offers the possibility of a complete and long-lasting remission in this disease, although only in a small percentage of patients. Intralesional IL-2 for in-transit metastases has a high complete response rate ranging from 40 to 100%.

By 2005 a number of new agents and novel approaches were under evaluation and showed promise.

In 2009 Clinical trial participation was considered the standard of care for metastatic melanoma.

Therapies for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.

Ongoing research is looking at treatment by adoptive cell transfer. For this purpose, application of prestimulated or modified T cells or dendritic cells is possible.

Confirmation of the clinical diagnosis is done with a skin biopsy. This is usually followed up with a wider excision of the scar or tumor. Depending on the stage, a sentinel lymph node biopsy is done, as well, although controversy exists around trial evidence for this procedure. Treatment of advanced malignant melanoma is performed from a multidisciplinary approach.

Therapies for metastatic melanoma include the biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.

Cimetidine works by slowing tumor growth; it is a histamine blocker that maintains the body’s immune response which aids in the killing of tumor cells. Cimetidine has not been proven to efficiently resolve tumors completely.

Cisplatin is a chemotherapy drug that is injected into the tumor itself; this drug is commonly used along with surgical removal. That being said, this drug has been shown to resolve tumors with or without surgical removal for at least 2 years.

The best treatment of lentigo maligna is not clear as it has not been well studied.

Standard excision is still being done by most surgeons. Unfortunately, the recurrence rate is high (up to 50%). This is due to the ill defined visible surgical margin, and the facial location of the lesions (often forcing the surgeon to use a narrow surgical margin). The use of dermatoscopy can significantly improve the surgeon's ability to identify the surgical margin. The narrow surgical margin used (smaller than the standard of care of 5 mm), combined with the limitation of the standard bread loafing technique of fixed tissue histology - result in a high "false negative" error rate, and frequent recurrences. Margin controlled (peripheral margins) is necessary to eliminate the false negative errors. If breadloafing is utilized, distances from sections should approach 0.1 mm to assure that the method approaches complete margin control.

Where the lesion is on the face and either large or 5mm margins are possible, a skin flap or skin graft may be indicated/required. Grafts have their own risks of failure and poor cosmetic outcomes. Flaps can require extensive incision resulting in long scars and may be better done by plastic surgeons (and possibly better again by those with extensive LM or "suspicious of early malignant melanoma" experience.

Mohs surgery has been done with cure rate reported to be 77%. The "double scalpel" peripheral margin controlled excision method approximates the Mohs method in margin control, but requires a pathologist intimately familiar with the complexity of managing the vertical margin on the thin peripheral sections and staining methods.

Some melanocytic nevi, and melanoma-in-situ (lentigo maligna) have resolved with an experimental treatment, imiquimod (Aldara) topical cream, an immune enhancing agent. In view of the very poor cure rate with standard excision, some surgeons combine the two methods: surgical excision of the lesion, then three months treatment of the area with imiquimod cream.

Studies seem to conflict about the level of certainty associated with using imiquimod.

Another treatment to be considered where standard margins cannot be achieved or cosmetics are a major consideration is ultra-soft x-ray/grenz-ray radiation.

In the very elderly or those with otherwise limited life expectancy, the impact of major day surgery for excision with 5mm margins and large skin flap could be worse than doing nothing or the possibility of failed treatments with imiquimod or Grenz ray.

The treatment protocol for uveal melanoma has been directed by many clinical studies, the most important being The Collaborative Ocular Melanoma Study (COMS). The treatment varies depending upon many factors, chief among them, the size of the tumor and results from testing of biopsied material from the tumor. Primary treatment can involve removal of the affected eye (enucleation); however, this is now reserved for cases of extreme tumor burden or other secondary problems. Advances in radiation therapies have significantly decreased the number of patients treated by enucleation in developed countries. The most common radiation treatment is plaque brachytherapy, in which a small disc-shaped shield (plaque) encasing radioactive seeds (most often Iodine-125, though Ruthenium-106 and Palladium-103 are also used) is attached to the outside surface of the eye, overlying the tumor. The plaque is left in place for a few days and then removed. The risk of metastasis after plaque radiotherapy is the same as that of enucleation, suggesting that micrometastatic spread occurs prior to treatment of the primary tumor. Other modalities of treatment include transpupillary thermotherapy, external beam proton therapy, resection of the tumor, Gamma Knife stereotactic radiosurgery or a combination of different modalities. Different surgical resection techniques can include trans-scleral partial choroidectomy, and transretinal endoresection.

Treatment of small melanomas is often not necessary, but large tumors can cause discomfort and are usually surgically removed. Cisplatin and cryotherapy can be used to treat small tumors less than 3 centimeters, but tumors may reoccur. Cimetidine, a histamine stimulator, can cause tumors to regress in some horses, but may take up to 3 months to produce results and multiple treatments may be needed throughout the horse's life. There are few viable treatment options for horses with metastatic melanoma. However, gene therapy injections utilizing interleukin-12 and 18-encoding DNA plasmids have shown promise in slowing the progression of tumors in patients with metastatic melanoma.

Appropriate sun-protective clothing, use of broad-spectrum (UVA/UVB) sunscreen with at least SPF 50, and avoidance of intense sun exposure may prevent skin cancer.

Most squamous cell carcinomas are removed with surgery. A few selected cases are treated with topical medication. Surgical excision with a free margin of healthy tissue is a frequent treatment modality. Radiotherapy, given as external beam radiotherapy or as brachytherapy (internal radiotherapy), can also be used to treat squamous cell carcinomas.

Mohs surgery is frequently utilized; considered the treatment of choice for squamous cell carcinoma of the skin, physicians have also utilized the method for the treatment of squamous cell carcinoma of the mouth, throat, and neck. An equivalent method of the CCPDMA standards can be utilized by a pathologist in the absence of a Mohs-trained physician. Radiation therapy is often used afterward in high risk cancer or patient types.

Electrodessication and curettage or EDC can be done on selected squamous cell carcinoma of the skin. In areas where SCC's are known to be non-aggressive, and where the patient is not immunosuppressed, EDC can be performed with good to adequate cure rate.

High-risk squamous cell carcinoma, as defined by those occurring around the eye, ear, or nose, is of large size, is poorly differentiated, and grows rapidly, requires more aggressive, multidisciplinary management.

Nodal spread:

1. Surgical block dissection if palpable nodes or in cases of Marjolin's ulcers but the benefit of prophylactic block lymph node dissection with Marjolin's ulcers is not proven.

2. Radiotherapy

3. Adjuvant therapy may be considered in those with high-risk SCC even in the absence of evidence for local mestastasis. Imiquimod (Aldara) has been used with success for squamous cell carcinoma "in situ" of the skin and the penis, but the morbidity and discomfort of the treatment is severe. An advantage is the cosmetic result: after treatment, the skin resembles normal skin without the usual scarring and morbidity associated with standard excision. Imiquimod is not FDA-approved for any squamous cell carcinoma.

In general, squamous cell carcinomas have a high risk of local recurrence, and up to 50% do recur. Frequent skin exams with a dermatologist is recommended after treatment.

Treatment depends on the thickness of the invasive component of the lentigo maligna. Treatment is essentially identical to other melanomas of the same thickness and stage.

Surgical resection of the tumor with wide margins remains the preferred method of treatment, and has shown the most success against the disease. Recently, limb-sparing surgery has been explored with moderate success.

In cases of advanced, recurrent, or metastasized disease, or if the tumor is inoperable, chemotherapy and radiation are the standard of care, although the overall success rates with these remains low.

Currently, there is no consensus regarding type or frequency of scans following diagnosis and treatment of the primary eye tumor. Of the 50% of patients who develop metastatic disease, more than 90% of patients will develop liver metastases. As such, the majority of surveillance techniques are focused on the liver. These include abdominal magnetic resonance imaging (MRI), abdominal ultrasound and liver function tests. The scientific community is currently working to develop guidelines, but until then, each patient must take into consideration their individual clinical situation and discuss appropriate surveillance with their doctors.

Some ophthalmologists have also found promise with the use of intravitreal avastin injections in patients suffering from radiation-induced retinopathy, a side effect of plaque brachytherapy treatment, as well as imaging surveillance with SD-OCT.

Treatment is dependent on type of cancer, location of the cancer, age of the person, and whether the cancer is primary or a recurrence. Treatment is also determined by the specific type of cancer. For a small basal-cell cancer in a young person, the treatment with the best cure rate (Mohs surgery or CCPDMA) might be indicated. In the case of an elderly frail man with multiple complicating medical problems, a difficult to excise basal-cell cancer of the nose might warrant radiation therapy (slightly lower cure rate) or no treatment at all. Topical chemotherapy might be indicated for large superficial basal-cell carcinoma for good cosmetic outcome, whereas it might be inadequate for invasive nodular basal-cell carcinoma or invasive squamous-cell carcinoma.. In general, melanoma is poorly responsive to radiation or chemotherapy.

For low-risk disease, radiation therapy (external beam radiotherapy or brachytherapy), topical chemotherapy (imiquimod or 5-fluorouracil) and cryotherapy (freezing the cancer off) can provide adequate control of the disease; all of them, however, may have lower overall cure rates than certain type of surgery. Other modalities of treatment such as photodynamic therapy, topical chemotherapy, electrodesiccation and curettage can be found in the discussions of basal-cell carcinoma and squamous-cell carcinoma.

Mohs' micrographic surgery (Mohs surgery) is a technique used to remove the cancer with the least amount of surrounding tissue and the edges are checked immediately to see if tumor is found. This provides the opportunity to remove the least amount of tissue and provide the best cosmetically favorable results. This is especially important for areas where excess skin is limited, such as the face. Cure rates are equivalent to wide excision. Special training is required to perform this technique. An alternative method is CCPDMA and can be performed by a pathologist not familiar with Mohs surgery.

In the case of disease that has spread (metastasized), further surgical procedures or chemotherapy may be required.

Treatments for metastatic melanoma include biologic immunotherapy agents ipilimumab, pembrolizumab, and nivolumab; BRAF inhibitors, such as vemurafenib and dabrafenib; and a MEK inhibitor trametinib.

2004 research showed that CCSK patients exhibit an improved relapse-free survival from a longer course of therapy when using vincristine, doxorubicin, and dactinomycin, but their long-term survival is unchanged compared with patients receiving 6 months of therapy.

It has been demonstrated that acral lentiginous melanoma has a poorer prognosis compared to that of cutaneous malignant melanoma (CMM).

Simple surgical excision is considered curative. Rare recurrences have been reported.

While sarcoids may spontaneously regress regardless of treatment in some instances, course and duration of disease is highly unpredictable and should be considered on a case-by-case basis taking into account cost of the treatment and severity of clinical signs. Surgical removal alone is not effective, with recurrence occurring in 50 to 64% of cases, but removal is often done in conjunction with other treatments. Topical treatment with products containing bloodroot extract (from the plant "Sanguinaria canadensis") for 7 to 10 days has been reported to be effective in removing small sarcoids, but the salve's caustic nature may cause pain and the sarcoid must be in an area where a bandage can be applied. Freezing sarcoids with liquid nitrogen (cryotherapy) is another affordable method, but may result in scarring or depigmentation. Topical application of the anti-metabolite 5-fluorouracil has also obtained favorable results, but it usually takes 30 to 90 days of repeated application before any effect can be realized. Injection of small sarcoids (usually around the eyes) with the chemotherapeutic agent cisplatin and the immunomodulator BCG have also achieved some success. In one trial, BCG was 69% effective in treating nodular and small fibroblastic sarcoids around the eye when repeatedly injected into the lesion and injection with cisplatin was 33% effective overall (mostly in horses with nodular sarcoids). However, BCG treatment carries a risk of allergic reaction in some horses and cisplatin has a tendency to leak out of sarcoids during repeated dosing. External beam radiation can also be used on small sarcoids, but is often impractical. Cisplatin electrochemotherapy (the application of an electrical field to the sarcoid after the injection of cisplatin, with the horse under general anesthesia), when used with or without prior surgery to remove the sarcoid, had a non-recurrence rate after four years of 97.9% in one retrospective study. There is a chance of sarcoid recurrence for all modalities even after apparently successful treatment. While sarcoids are not fatal, large aggressive tumors that destroy surrounding tissue can cause discomfort and loss of function and be resistant to treatment, making euthanasia justifiable in some instances. Sarcoids may be the most common skin-related reason for euthanasia.

Currently, surgical excision is the most common form of treatment for skin cancers. The goal of reconstructive surgery is restoration of normal appearance and function. The choice of technique in reconstruction is dictated by the size and location of the defect. Excision and reconstruction of facial skin cancers is generally more challenging due to presence of highly visible and functional anatomic structures in the face.

When skin defects are small in size, most can be repaired with simple repair where skin edges are approximated and closed with sutures. This will result in a linear scar. If the repair is made along a natural skin fold or wrinkle line, the scar will be hardly visible. Larger defects may require repair with a skin graft, local skin flap, pedicled skin flap, or a microvascular free flap. Skin grafts and local skin flaps are by far more common than the other listed choices.

Skin grafting is patching of a defect with skin that is removed from another site in the body. The skin graft is sutured to the edges of the defect, and a bolster dressing is placed atop the graft for seven to ten days, to immobilize the graft as it heals in place. There are two forms of skin grafting: split thickness and full thickness. In a split thickness skin graft, a shaver is used to shave a layer of skin from the abdomen or thigh. The donor site regenerates skin and heals over a period of two weeks. In a full thickness skin graft, a segment of skin is totally removed and the donor site needs to be sutured closed.

Split thickness grafts can be used to repair larger defects, but the grafts are inferior in their cosmetic appearance. Full thickness skin grafts are more acceptable cosmetically. However, full thickness grafts can only be used for small or moderate sized defects.

Local skin flaps are a method of closing defects with tissue that closely matches the defect in color and quality. Skin from the periphery of the defect site is mobilized and repositioned to fill the deficit. Various forms of local flaps can be designed to minimize disruption to surrounding tissues and maximize cosmetic outcome of the reconstruction. Pedicled skin flaps are a method of transferring skin with an intact blood supply from a nearby region of the body. An example of such reconstruction is a pedicled forehead flap for repair of a large nasal skin defect. Once the flap develops a source of blood supply form its new bed, the vascular pedicle can be detached.

Staging and treatment are generally handled by an oncologist familiar with gynecologic cancer. Surgery is a mainstay of therapy depending on anatomical staging and is usually reserved for cancers that have not spread beyond the vulva. Surgery may involve a wide local excision, radical partial vulvectomy, or radical complete vulvectomy with removal of vulvar tissue, inguinal and femoral lymph nodes. In cases of early vulvar cancer, the surgery may be less extensive and consist of wide excision or a simple vulvectomy. Surgery is significantly more extensive when the cancer has spread to nearby organs such as the urethra, vagina, or rectum. Complications of surgery include wound infection, sexual dysfunction, edema and thrombosis, as well as lymphedema secondary to dissected lymph nodes.

Sentinel lymph node (SLN) dissection is the identification of the main lymph node(s) draining the tumor, with the aim of removing as few nodes as possible, decreasing the risk of adverse effects. Location of the sentinel node(s) may require the use of technetium(99m)-labeled nano-colloid, or a combination of technetium and 1% isosulfan blue dye, wherein the combination may reduce the number of women with "'missed"' groin node metastases compared with technetium only.

Radiation therapy may be used in more advanced vulvar cancer cases when disease has spread to the lymph nodes and/or pelvis. It may be performed before or after surgery. Chemotherapy is not usually used as primary treatment but may be used in advanced cases with spread to the bones, liver or lungs. It may also be given at a lower dose together with radiation therapy.

Women with vulvar cancer should have routine follow-up and exams with their oncologist, often every 3 months for the first 2–3 years after treatment. They should not have routine surveillance imaging to monitor the cancer unless new symptoms appear or tumor markers begin rising. Imaging without these indications is discouraged because it is unlikely to detect a recurrence or improve survival and is associated with its own side effects and financial costs.