This form of cancer is often seen in those who chew tobacco or use snuff orally, so much so that it is sometimes referred to as "Snuff dipper's cancer." Chewing betel nuts is an additional risk factor commonly seen in Taiwan.

Diagnosis is confirmed via biopsy of the tissue(s) suspected to be affected by SCC. For the skin, look under skin biopsy.

The pathological appearance of a squamous cell cancer varies with the depth of the biopsy. For that reason, a biopsy including the subcutaneous tissue and basalar epithelium, to the surface is necessary for correct diagnosis. The performance of a shave biopsy (see skin biopsy) might not acquire enough information for a diagnosis. An inadequate biopsy might be read as actinic keratosis with follicular involvement. A deeper biopsy down to the dermis or subcutaneous tissue might reveal the true cancer. An excision biopsy is ideal, but not practical in most cases. An incisional or punch biopsy is preferred. A shave biopsy is least ideal, especially if only the superficial portion is acquired.

The differential for OSSN includes pterygium, pingueculum, papilloma, solar keratosis, lipoma, lymphoma, chronic blepharoconjunctivitis, inflammation, melanoma, ocular pannus, pyogenic granuloma, kaposi sarcoma, keratocanthoma, mucoepidermoid carcinoma, pseudoepitheliomatous hyperplasia, and adenocarcinoma. While confocal microscopy can be used for diagnosis, biopsy is considered the standard, especially before treatment with a cytotoxic medication.

Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.

Surgical excision or laser therapy are possible treatments. Surgical excision alone was effective for controlling VC, but elective neck dissection was not necessary even in patients in the advanced stages.

The long-term outcome of squamous cell carcinomas is dependent upon several factors: the sub-type of the carcinoma, available treatments, location(s) and severity, and various patient health-related variables (accompanying diseases, age, etc.). Generally, the long-term outcome is positive, as less than 4% of Squamous cell carcinoma cases are at risk of metastasis. Some particular forms of squamous cell carcinomas have a higher mortality rate. One study found squamous cell carcinoma of the penis had a much greater rate of mortality than some other forms of squamous cell carcinoma, that is, about 23%, although this relatively high mortality rate may be associated with possibly latent diagnosis of the disease due to patients avoiding genital exams until the symptoms are debilitating, or refusal to submit to a possibly scarring operation upon the genitalia. Squamous cell carcinoma occurring in the organ transplant population is also associated with a higher risk of mortality.

The first step to diagnosing tonsil carcinoma is to obtain an accurate history from the patient. The physician will also examine the patient for any indicative physical signs. A few tests then, maybe conducted depending on the progress of the disease or if the doctor feels the need for. The tests include:

Fine needle aspiration, blood tests, MRI, x-rays and PET scan.

The prognosis of EMECL is relatively good, and considerably better than most other forms of NSCLC. The skull and dura are possible sites for metastasis from pulmonary EMC. The MIB-1 index is a predictive marker of malignant potential.

The basis of deciding the T stage depends on physical examination and imaging of the tumor.

Most conjunctival 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.

Overall, five-year survival rates for vulvar cancer are around 78% but may be affected by individual factors including cancer stage, cancer type, patient age and general medical health. Five-year survival is greater than 90% for patients with stage I lesions but decreases to 20% when pelvic lymph nodes are involved. Lymph node involvement is the most important predictor of prognosis. Thus, early diagnosis is important.

EMECL is staged in the same manner as other non-small cell lung carcinomas, based on the TNM (Tumor-Node-Metastasis) staging system.

There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:

- Wide local excision—the tumor and some surrounding healthy tissue are removed

- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible

- Laser surgery—laser light is used to burn or cut away cancerous cells

- Circumcision—cancerous foreskin is removed

- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.

Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.

In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.

Diagnostic tests typically include complete blood tests, urinalysis, urine culture, X-rays of the abdomen and chest, and bladder imaging. The definitive diagnosis of bladder cancer will require a tissue biopsy and subsequent examination of the cells under the microscope.

Anatomical staging supplemented preclinical staging starting in 1988. FIGO’s revised TNM classification system uses tumor size (T), lymph node involvement (N) and presence or absence of metastasis (M) as criteria for staging. Stages I and II describe the early stages of vulvar cancer that still appear to be confined to the site of origin. Stage III cancers include greater disease extension to neighboring tissues and inguinal lymph nodes on one side. Stage IV indicates metastatic disease to inguinal nodes on both sides or distant metastases.

Because most bladder cancers are invasive into the bladder wall, surgical removal is usually not possible. The majority of transitional cell carcinomas are treated with either traditional chemotherapy or nonsteroidal anti-inflammatory drugs.

When associated with the prostate, squamous cell carcinoma is very aggressive in nature. It is difficult to detect as there is no increase in prostate specific antigen levels seen; meaning that the cancer is often diagnosed at an advanced stage.

It is important to exclude a tumor which is directly extending into the ear canal from the parotid salivary gland, especially when dealing with an adenoid cystic or mucoepidermoid carcinoma. This can be eliminated by clinical or imaging studies. Otherwise, the histologic differential diagnosis includes a ceruminous adenoma (a benign ceruminous gland tumor) or a neuroendocrine adenoma of the middle ear (middle ear adenoma).

NMC when viewed microscopically, are poorly differentiated carcinomas which show abrupt transitions to islands of well-differentiated squamous epithelium. This tumor pattern is not specific or unique to NUT midline carcinoma, but this pattern is most suggestive of the diagnosis. The neoplastic cells will show a positive reaction with various cytokeratins, p63, CEA, and CD34 immunohistochemistry. However, the NUT antibody confirms the diagnosis (although only available in a limited number of laboratories).

The differential diagnosis is quite wide, but it is important to consider this tumor type when seeing a poorly differentiated tumor that shows abrupt areas of keratinization. Other tumors included in the differential diagnosis are sinonasal undifferentiated carcinomas, Ewing sarcoma/Primitive neuroectodermal tumor, leukemia, rhabdomyosarcoma, and melanoma. When NUT midline carcinoma is seen in the head and neck, the squamous lining of the cavities may be entrapped by the neoplastic cells, and so it is important to document the carcinoma cells in the rest of the tumor by a variety of stains (including cytokeratin or p63). One of the most helpful and characteristic findings is the focal abrupt squamous differentiation, where stratification and gradual differentiation are absent, resembling a Hassall corpuscle of the thymus.

The defining feature of NMCs is rearrangement of the "NUT" gene.

Most common is a translocation involving the BRD4 gene and NUT gene (t(15;19)(q13;p13.1)).

Vaginal squamous cell carcinoma spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer.

Keratoacanthoma presents as a fleshy, elevated and nodular lesion with an irregular crater shape and a characteristic central hyperkeratotic core. Usually the patient will notice a rapidly growing dome-shaped tumor on sun-exposed skin.

If the entire lesion is removed, the pathologist will probably be able to differentiate between keratoacanthoma and squamous cell carcinoma. If only part of the lesion is removed, confident diagnosis may be impossible.

Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.

Staging of nasopharyngeal carcinoma is based on clinical and radiologic examination. Most patients present with Stage III or IV disease.

Stage I is a small tumor confined to nasopharynx.

Stage II is a tumor extending in the local area, or that with any evidence of limited neck (nodal) disease.

Stage III is a large tumor with or without neck disease, or a tumor with bilateral neck disease.

Stage IV is a large tumor involving intracranial or infratemporal regions, an extensive neck disease, and/or any distant metastasis.

External beam radiotherapy has been used in one person to prevent the relapse and growth of tumor metastases to the head and neck regions. The prophylactic applications of radiation have been noted as “encouraging” in this one case, reducing some tumors and eliminating others.

Another study with a couple of the same authors found that radiotherapy after surgery helped with the reduction and cure of head and neck tumors in additional cases. The researchers suggest that external beam radiotherapy should be part of the treatment course for patients who have or at risk of developing tumors in the head and neck areas.

In the treatment of Kangri cancer, surgery is, most often, the first-line course of action to remove the primary tumor.