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.

Cancer screening uses medical tests to detect disease in large groups of people who have no symptoms. For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life. This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). High risk people are those age 55–74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.

CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there are about 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with follow up. Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.

The United States Preventive Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 and 80 years old until a person has not been smoking for more than 15 years. Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option. The English National Health Service was in 2014 re-examining the evidence for screening.

Definitive diagnosis of Merkel cell carcinoma (MCC) requires examination of biopsy tissue. An ideal biopsy specimen is either a punch biopsy or a full-thickness incisional biopsy of the skin including full-thickness dermis and subcutaneous fat. In addition to standard examination under light microscopy, immunohistochemistry (IHC) is also generally required to differentiate MCC from other morphologically similar tumors such as small cell lung cancer, the small cell variant of melanoma, various cutaneous leukemic/lymphoid neoplasms, and Ewing's sarcoma. Similarly, most experts recommend longitudinal imaging of the chest, typically a CT scan, to rule out that the possibility that the skin lesion is a cutaneous metastasis of an underlying small cell carcinoma of the lung.

Unlike its differentiated counterparts, anaplastic thyroid cancer is highly unlikely to be curable either by surgery or by any other treatment modality, and is in fact usually unresectable due to its high propensity for invading surrounding tissues.

Palliative treatment consists of radiation therapy usually combined with chemotherapy.

New drugs, such as fosbretabulin (a type of combretastatin), bortezomib and TNF-Related Apoptosis Induced Ligand (TRAIL), are however being under investigation "in vitro" and in human clinical studies. Based on encouraging Phase I and II clinical trial results with fosbretabulin, a type of drug that selectively destroys tumor blood vessels, a large, multi-national clinical trial is being undertaken to determine whether the drug can extend the survival of patients with ATC.

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 role of external beam radiotherapy (EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.

The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.

Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.

Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.

Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.

This type of cancer occurs most often in Caucasians between 60 and 80 years of age, and its rate of incidence is about twice as high in males as in females. There are roughly 1,500 new cases of MCC diagnosed each year in the United States, as compared to around 60,000 new cases of melanoma and over 1 million new cases of nonmelanoma skin cancer. MCC is sometimes mistaken for other histological types of cancer, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, lymphoma, and small cell carcinoma, or as a benign cyst. Researchers believe that exposure to sunlight or ultraviolet light (such as in a tanning bed) may increase the risk of developing this disease. Similar to melanoma, the incidence of MCC in the US is increasing rapidly.

Immunosuppression can profoundly increase the odds of developing Merkel-cell carcinoma. Merkel-cell carcinoma occurs 30 times more often in people with chronic lymphocytic leukemia and 13.4 times more often in people with advanced HIV as compared to the general population; solid organ transplant recipients have a 10-fold increased risk compared to the general population.

It is very difficult to treat glioblastoma due to several complicating factors:

- The tumor cells are very resistant to conventional therapies.

- The brain is susceptible to damage due to conventional therapy.

- The brain has a very limited capacity to repair itself.

- Many drugs cannot cross the blood–brain barrier to act on the tumor.

Treatment of primary brain tumors and brain metastases consists of both symptomatic

and palliative therapies.

In the detection of bone metastases, skeletal scintigraphy (bone scan) is very sensitive and is recommended as the first imaging study in asymptomatic individuals with suspected breast-cancer metastases. X-ray radiography is recommended if there is abnormal radionuclide uptake from the bone scan and in assessing the risk of pathological fractures, and is recommended as the initial imaging study in patients with bone pain. MRI or the combination PET-CT may be considered for cases of abnormal radionuclide uptake on bone scan, when radiography does not give an acceptably clear result.

The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies suggest that people who eat diets with a higher proportion of vegetables and fruit tend to have a lower risk, but this may be due to confounding—with the lower risk actually due to the association of a high fruit/vegetables diet with less smoking. Several rigorous studies have not demonstrated a clear association between diet and lung cancer risk, although meta-analysis that accounts for smoking status may show benefit from a healthy diet.

Early detection is key. Untreated patients usually live 5 to 8 months after diagnosis.

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

When viewed with MRI, glioblastomas often appear as ring-enhancing lesions. The appearance is not specific, however, as other lesions such as abscess, metastasis, tumefactive multiple sclerosis, and other entities may have a similar appearance. Definitive diagnosis of a suspected GBM on CT or MRI requires a stereotactic biopsy or a craniotomy with tumor resection and pathologic confirmation. Because the tumor grade is based upon the most malignant portion of the tumor, biopsy or subtotal tumor resection can result in undergrading of the lesion. Imaging of tumor blood flow using perfusion MRI and measuring tumor metabolite concentration with MR spectroscopy may add value to standard MRI in select cases by showing increased relative cerebral blood volume and increased choline peak respectively, but pathology remains the gold standard for diagnosis and molecular characterization.

It is important to distinguish primary glioblastoma from secondary glioblastoma. These tumors occur spontaneously ("de novo") or have progressed from a lower-grade glioma, respectively. Primary glioblastomas have a worse prognosis, different tumor biology and may have a different response to therapy, which makes this a critical evaluation to determine patient prognosis and therapy. Over 80% of secondary glioblastoma carries a mutation in "IDH1", whereas this mutation is rare in primary glioblastoma (5–10%). Thus, "IDH1" mutations are a useful tool to distinguish primary and secondary glioblastomas since histopathologically they are very similar and the distinction without molecular biomarkers is unreliable.

Two cell types can be seen microscopically in synovial sarcoma. One fibrous type, known as a spindle or sarcomatous cell, is relatively small and uniform, and found in sheets. The other is epithelial in appearance. Classical synovial sarcoma has a biphasic appearance with both types present. Synovial sarcoma can also appear to be poorly differentiated or to be monophasic fibrous, consisting only of sheets of spindle cells. Some authorities state that, extremely rarely, there can be a monophasic epithelial form which causes difficulty in differential diagnosis. Depending on the site, there is similarity to biphenotypic sinonasal sarcoma, although the genetic findings are distinctive.

Like other soft tissue sarcomas, there is no universal grading system for reporting histopathology results. In Europe, the Trojani or French system is gaining in popularity while the NCI grading system is more common in the United States. The Trojani system scores the sample, depending on tumour differentiation, mitotic index, and tumour necrosis, between 0 and 6 and then converts this into a grade of between 1 and 3, with 1 representing a less aggressive tumour. The NCI system is also a three-grade one, but takes a number of other factors into account.

Esthesioneuroblastoma can resemble small blue cell tumors like squamous cell carcinoma, sinonasal undifferentiated carcinoma, extranodal NK/T cell lymphoma, nasal type, rhabdomyosarcoma, Ewing/PNET, mucosal malignant melanoma and neuroendocrine carcinomas (NEC) that occur in the intranasal tract. Compared to other tumors in the region, esthesioneuroblastoma has the best prognosis, with an overall 5 year survival rate of 60-80%. Fewer than 700 cases have been documented in the United States alone. Esthesioneuroblastoma is characterized by neurofibrillary stroma and neurosecretary granules that are not seen concurrently by any other pathologies in the region. Histological tests such as keratin, CK5/6, S-100 protein or NSE can be run to further differentiate esthesioneuroblastoma from other tumors.

Esthesioneuroblastoma is a slow developing but malignant tumor with high reoccurrence rates because of its anatomical position. The tumor composition, location and metastatic characteristics as well as the treatment plan determine prognosis. Common clinical classification systems for esthesioneuroblastoma include the Kadish classification and the Dulguerov classfictation. Histopathological characteristics on top of Kadish classification can further determine cancer prognosis. In severe, Kadish class C tumors, Haym's grades of pathology are important for prognosis. Patients with low grade Kadish class C tumors have a 10-year survival rate of 86 percent compared to patients with high grade class C tumors who have a survival rate of 28 percent. Surgically treated patients with high grade tumors are more likely to experience leptomeningeal metastases or involvement of the cerebral spinal fluid unlike patients with low grade tumors who usually only see local recurrence. Survival rates for treated esthesioneuroblastoma are best for surgery with radiotherapy (65%), then for radiotherapy and chemotherapy (51%), just surgery (48%), surgery, radiotherapy and chemotherapy (47) and finally just radiotherapy (37%). From the literature, radiotherapy and surgery seem to boast the best outcome for patients. However, it is important to understand that to some degree, prognosis is related to tumor severity. More progressed, higher grade tumors would result in chemotherapy or radiotherapy as the only treatment. It is no surprise that the prognosis would be worse in these cases.

The diagnosis of synovial sarcoma is typically made based on histology and is confirmed by the presence of t(X;18) chromosomal translocation.

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.

Clinically symptomatic CNS metastases are reported in 10–15% of patients with metastatic breast cancer; in large autopsy studies, up to 40% of women who died of metastatic breast cancer were reported to have at least one brain metastasis. CNS metastases are often viewed by patients and doctors as a late complication of metastatic breast cancer for which few effective treatments exist. In most cases, CNS involvement occurs after metastatic dissemination to the bones, liver and/or lungs has already occurred; for that reason, many patients already have refractory, terminal breast cancer by the time they are diagnosed with brain metastases. The diagnosis of brain metastases from breast cancer relies mainly on patient-reported symptoms and neuroimaging. The role of imaging in patients with suspected brain metastases is a very good modality to aid in diagnosis. According to Weil et al., 2005, neuroimaging such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) prove to be very effective in the diagnosis of brain and central nervous system metastases.

Symptoms of brain metastases from breast cancer are:

- new-onset headache

- changes in mental status, cognition and behavior

- ataxia

- cranial neuropathy, which may cause diplopia and Bell's palsy

- vomiting and nausea

- deficits in sensation, motor function, and speech

Of all brain-metastatic patients, those with a controlled extra-cranial tumor, age less than 65 years and a favorable general performance (Karnofsky performance status ≥70) fare best; older patients with a Karnofsky performance status below 70 do poorly. Effective treatments for brain metastases from breast cancer exist, although symptomatic therapy alone may be chosen for those with poor performance status. Corticosteroids are crucial to the treatment of brain metastases from any source (including the breast), and are effective in reducing peri-tumoral edema and providing symptomatic relief. Chemotherapy has not been found to be effective in the treatment of brain metastases from breast cancer, due to the inability of most chemotheraputic agents to penetrate the blood–brain barrier. Whole-brain radiation may provide a median survival of 4 to 5 months, which can be further extended by months with stereotactic surgery. Several non-randomized studies have suggested that stereotactic surgery may provide a nearly equivalent outcome, compared with surgery followed by whole brain-irradiation. Surgery tends to reduce symptoms quickly and prolong life, with an improved quality of life. Multiple metastases (up to three) may be removed surgically with a risk similar to that of a single lesion, providing similar benefits. Adjuvant radiotherapy follows surgical resection; this combined approach has been shown to prolong median survival up to 12 months, depending on the factors noted above. There is evidence that surgery may be useful in select patients with recurrent brain metastases. Mean survival from diagnosis of a brain metastasis varies between studies, ranging from 2 to 16 months (depending on involvement of the CNS, the extent of the extra-cranial metastatic disease, and the treatment applied). The mean 1-year survival is estimated at 20%. Improvements in the treatment of brain metastases are clearly needed.

Prognosis is excellent if the appropriate method of treatment is used in early primary basal-cell cancers. Recurrent cancers are much harder to cure, with a higher recurrent rate with any methods of treatment. Although basal-cell carcinoma rarely metastasizes, it grows locally with invasion and destruction of local tissues. The cancer can impinge on vital structures like nerves and result in loss of sensation or loss of function or rarely death. The vast majority of cases can be successfully treated before serious complications occur. The recurrence rate for the above treatment options ranges from 50 percent to 1 percent or less.

The following methods are employed in the treatment of basal-cell carcinoma (BCC):

All in all, small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low.

In "limited-stage" disease, median survival with treatment is 14–20 months, and about 20% of patients with limited-stage small-cell lung carcinoma live 5 years or longer. Because of its predisposition for early metastasis, the prognosis of SCLC is poor, with only 10% to 15% of patients surviving 3 years.

The prognosis is far more grim in "extensive-stage" small-cell lung carcinoma; with treatment, median survival is 8–13 months; only 1–5% of patients with extensive-stage small-cell lung carcinoma treated with chemotherapy live 5 years or longer.

Micrometastasis is a form of metastasis (the spread of a cancer from its original location to other sites in the body) in which the newly formed tumors are too minuscule to be detected.

Adjuvant chemotherapy and adjuvant radiotherapy are directed at killing any micrometastases, thus preventing relapse (regrowth of the cancer) and the (likely) death of the patient. Early detection of micrometastases could identify the patients who are most (and least) likely to benefit from adjuvant therapy.

In addition to being named based on the tissue of origin, sarcomas are also assigned a grade (low, intermediate, or high) based on the presence and frequency of certain cellular and subcellular characteristics associated with malignant biological behavior. Low grade sarcomas are usually treated surgically, although sometimes radiation therapy or chemotherapy are used. Intermediate and high grade sarcomas are more frequently treated with a combination of surgery, chemotherapy and/or radiation therapy. Since higher grade tumors are more likely to undergo metastasis (invasion and spread to locoregional and distant sites), they are treated more aggressively. The recognition that many sarcomas are sensitive to chemotherapy has dramatically improved the survival of patients. For example, in the era before chemotherapy, long-term survival for patients with localized osteosarcoma was only approximately 20%, but now has risen to 60–70%.

Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).

However, the influential WHO Classification (published in 2001) placed a greater emphasis on cell lineage.

Relative proportions of hematological malignancies in the United States