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).

Generally, there is a good prognosis for low-grade tumors, and a poor prognosis for high-grade tumors.

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.

There are many diagnostic methods that can be used to determine the type of salivary gland tumour and if it is benign or malignant. Examples of diagnostic methods include:

Physical exam and history: An exam of the body to check general signs of health. The head, neck, mouth, and throat will be checked for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.

Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. For salivary gland cancer, an endoscope is inserted into the mouth to look at the mouth, throat, and larynx. An endoscope is a thin, tube-like instrument with a light and a lens for viewing.

MRI

Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.

Fine needle aspiration (FNA) biopsy: The removal of tissue or fluid using a thin needle. An FNA is the most common type of biopsy used for salivary gland cancer, and has been shown to produce accurate results when differentiating between benign and malignant tumours.

Radiographs: An OPG (orthopantomogram) can be taken to rule out mandibular involvement. A chest radiograph may also be taken to rule out any secondary tumours.

Ultrasound: Ultrasound can be used to initially assess a tumour that is located superficially in either the submandibular or parotid gland. It can distinguish an intrinsic from an extrinsic neoplasm. Ultrasonic images of malignant tumours include ill defined margins.

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

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.

Wide, radical, complete surgical excision is the treatment of choice, with free surgical margins to achieve the best outcome and lowest chance of recurrence. Radiation is only used for palliation. In general, there is a good prognosis, although approximately 50% of patients die from disease within 3–10 years of presentation.

MCACL has a much more favorable prognosis than most other forms of adenocarcinoma and most other NSCLC's. Cases have been documented of continued growth of these lesions over a period of 10 years without symptoms or metastasis. The overall mortality rate appears to be somewhere in the vicinity of 18% to 27%, depending on the criteria that are used to define this entity.

Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumour's tendency to spread along nerve tracts. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.

Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case by case basis, as there is limited trial data on the positive effects of chemotherapy. Clinical studies are ongoing, however.

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 US Preventive Services Task Force (USPSTF) in 2013 stated evidence was insufficient to determine the balance of benefits and harms of screening for oral cancer in adults without symptoms by primary care providers. The American Academy of Family Physicians comes to similar conclusions while the American Cancer Society recommends that adults over 20 years who have periodic health examinations should have the oral cavity examined for cancer. The American Dental Association recommends that providers remain alert for signs of cancer during routine examinations.

There are a variety of screening devices, however, there is no evidence that routine use of these devices in general dental practice is helpful. However, there are compelling reasons to be concerned about the risk of harm this device may cause if routinely used in general practice. Such harms include false positives, unnecessary surgical biopsies and a financial burden on the patient.

Early diagnosis of oral cancer patients would decrease mortality and help to improve treatment. Oral surgeons and dentists can diagnose these patients in the early stages. Health providers, dentists, and oral surgeons shall have high knowledge and awareness that would help them to provide better diagnosis for oral cancer patients. An examination of the mouth by the health care provider, dentist, oral surgeons shows a visible and/or palpable (can be felt) lesion of the lip, tongue, or other mouth area. The lateral/ventral sides of the tongue are the most common sites for intraoral SCC. As the tumor enlarges, it may become an ulcer and bleed. Speech/talking difficulties, chewing problems, or swallowing difficulties may develop. A feeding tube is often necessary to maintain adequate nutrition. This can sometimes become permanent as eating difficulties can include the inability to swallow even a sip of water. The doctor can order some special investigations which may include a chest x-ray, CT or MRI scans, and tissue biopsy.

While a dentist, physician or other health professional may suspect a particular lesion is malignant, there is no way to tell by looking alone - since benign and malignant lesions may look identical to the eye. A non-invasive brush biopsy (BrushTest) can be performed to rule out the presence of dysplasia (pre-cancer) and cancer on areas of the mouth that exhibit an unexplained color variation or lesion. The only definitive method for determining if cancerous or precancerous cells are present is through biopsy and microscopic evaluation of the cells in the removed sample. A tissue biopsy, whether of the tongue or other oral tissues and microscopic examination of the lesion confirm the diagnosis of oral cancer or precancer.

Treatment may include the following:

- Surgery with or without radiation

- Radiotherapy

Fast neutron therapy has been used successfully to treat salivary gland tumors, and has shown to be significantly more effective than photons in studies treating unresectable salivary gland tumors.

- Chemotherapy

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.

For treatment purposes, MCACL has been traditionally considered a non-small cell lung carcinoma (NSCLC). Complete radical surgical resection is the treatment of choice.

There is virtually no data regarding new molecular targets or targeted therapy in the literature to date. Iwasaki and co-workers failed to find mutations of the epidermal growth factor receptor (EGFR) or the cellular Kirsten rat sarcoma virus oncogene "K-ras" in one reported case.

Occurs in adults, with peak incidence from 20–40 years of age. A causal link with cytomegalovirus (CMV) has been strongly implicated in a 2011 research.

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.

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.

Avoidance of recognised risk factors (as described above) is the single most effective form of prevention. Regular dental examinations may identify pre-cancerous lesions in the oral cavity.

When diagnosed early, oral, head and neck cancers can be treated more easily and the chances of survival increase tremendously. As of 2017 it was not known if existing HPV vaccines can help prevent head and neck cancer.

Human papillomavirus infection (HPV) has been associated with SCC of the oropharynx, lung, fingers and anogenital region.

HCCC consist of cells with abundant clear cytoplasm, arranged in cords, trabeculae or clusters in a hyalinized stroma. Nuclear pleomorphism is usually minimal and mitoses are infrequently seen.

Owing to their glycogen content, which explains the "clear" appearance under the microscope, tumour cells stain with PAS. Immunostains for S100 and smooth muscle actin (SMA) are typically negative, but positive for cytokeratins and epithelial membrane antigen (EMA).

HCCCs typically have a recurrent chromosomal translocation, t(12;22), involving the genes EWSR1 and ATF1. The same translocation is seen in clear cell sarcoma.

The histologic differential diagnosis includes mucoepidermoid carcinoma (clear cell variant), acinic cell carcinoma (clear cell variant), epithelial-myoepithelial carcinoma and metastatic clear cell carcinoma.

Treatment involves biopsy of the lesion to identify extent of dysplasia. Complete excision of the lesion is sometimes advised depending on the histopathology found in the biopsy. Even in these cases, recurrence of the erythroplakia is common and, thus, long-term monitoring is needed.

Lymphoma is the most common type of blood-related cancer in horses and while it can affect horses of all ages, it typically occurs in horses aged 4–11 years.

There are many other conditions that are similar in appearance and must be ruled out before a diagnosis of erythroplakia is made (see table). Sometimes, a diagnosis is delayed for up to two weeks in order to see if the lesion spontaneously regresses on its own or if another cause can be found. Erythroplakia frequently is associated with dysplasia, and is thus a precancerous lesion.

The treatment is simple excision and exclusion of a malignant neoplasm.