Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (usually excisional biopsy with microscopic examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium scan may be used instead of a PET scan.

Treatment of Hodgkin's disease has been improving over the past few decades. Recent trials that have made use of new types of chemotherapy have indicated higher survival rates than have previously been seen. In one recent European trial, the 5-year survival rate for those patients with a favorable prognosis (FFP) was 98%, while that for patients with worse outlooks was at least 85%.

In 1998, an international effort identified seven prognostic factors that accurately predict the success rate of conventional treatment in patients with locally extensive or advanced stage Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years was directly related to the number of factors present in a patient. The 5-year FFP for patients with zero factors is 84%. Each additional factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for a patient with 5 or more factors is 42%.

The adverse prognostic factors identified in the international study are:

- Age ≥ 45 years

- Stage IV disease

- Hemoglobin < 10.5 g/dl

- Lymphocyte count < 600/µl or < 8%

- Male

- Albumin < 4.0 g/dl

- White blood count ≥ 15,000/µl

Other studies have reported the following to be the most important adverse prognostic factors: mixed-cellularity or lymphocyte-depleted histologies, male sex, large number of involved nodal sites, advanced stage, age of 40 years or more, the presence of B symptoms, high erythrocyte sedimentation rate, and bulky disease (widening of the mediastinum by more than one third, or the presence of a nodal mass measuring more than 10 cm in any dimension.)

More recently, use of positron emission tomography (PET) early after commencing chemotherapy has demonstrated to have powerful prognostic ability. This enables assessment of an individual's response to chemotherapy as the PET activity switches off rapidly in patients who are responding. In this study, after two cycles of ABVD chemotherapy, 83% of patients were free of disease at 3 years if they had a negative PET versus only 28% in those with positive PET scans. This prognostic power exceeds conventional factors discussed above. Several trials are underway to see if PET-based risk adapted response can be used to improve patient outcomes by changing chemotherapy early in patients who are not responding.

Diagnosis usually occurs at an early stage of disease progression.

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Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

The factors of poor prognosis for patients with thyroid lymphoma are advanced stage of the tumor, large size (>10 cm) as well as spreading to mediastinum. The overall survival for primary thyroid lymphoma is 50% to 70%, ranging from 80% in stage IE to less than 36% in stage IIE and IVE in 5 years.

Of all cancers involving the same class of blood cell (lymphoproliferative disorders), 22% of cases are follicular lymphomas.

Median survival is around 10 years, but the range is wide, from less than one year, to more than 20 years. Some patients may never need treatment. The overall survival rate at five years is 72–77%. Recent advances and addition of Rituximab, improved median survival. Recent reports for the period 1986 and 2012 estimates median survival of over 20 years.

Nevertheless, the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's versus non-Hodgkin lymphomas by major cancer agencies, including the US National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.

Biopsy of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound and bone marrow biopsy reveal other locations of the cancer. There are now a range of blood tests that can be utilised to aid in the diagnosis of lymphoma. Flow cytometry detects antibodies linked to tumour cell surface antigens in fluid samples or cell suspensions. Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) identifies circulating tumour cells based on unique genetic sequences. The canine Lymphoma Blood Test (cLBT) measures multiple circulating biomarkers and utilises a complex algorithm to diagnose lymphoma. This test utilises the acute phase proteins (C-Reactive Protein and Haptoglobin). In combination with basic clinical symptoms, it gives in differential diagnosis the sensitivity 83.5% and specificity 77%. The TK canine cancer panel is an indicator of general neoplastic disease. The stage of the disease is important to treatment and prognosis. Certain blood tests have also been shown to be prognostic.

The stage of the disease is important to treatment and prognosis.

- Stage I - only one lymph node or lymphoid tissue in one organ involved.

- Stage II - lymph nodes in only one area of the body involved.

- Stage III - generalized lymph node involvement.

- Stage IV - any of the above with liver or spleen involvement.

- Stage V - any of the above with blood or bone marrow involvement.

Each stage is divided into either "substage a", those without systemic symptoms; or "substage b", those with systemic symptoms such as fever, loss of appetite, weight loss, and fatigue.

The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.

While the bone marrow is commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. Immunohistochemistry can aid in the detection of this lymphoma.

Primary cerebral lymphoma (or "primary central nervous system lymphoma") is a form of NHL. It is very rare in immunocompetent people, with an incidence of 5–30 cases per million person-years. However the incidence in immunocompromised individuals is greatly increased, up to 100 per million person-years.

Primary cerebral lymphoma is strongly associated with Epstein–Barr virus (EBV). The presence of EBV DNA in cerebrospinal fluid is highly suggestive of primary cerebral lymphoma.

Treatment of AIDS patients with antiretroviral drugs reduces the incidence of primary cerebral lymphoma.

The incidence of Hodgkin's disease in the general population is about 10–30 per million person-years. This increases to 170 per million person-years in HIV positive patients.

Lymphoma is common in ferrets and is the most common cancer in young ferrets. There is some evidence that a retrovirus may play a role in the development of lymphoma like in cats. The most commonly affected tissues are the lymph nodes, spleen, liver, intestine, mediastinum, bone marrow, lung, and kidney.

In young ferrets, the disease progresses rapidly. The most common symptom is difficulty breathing caused by enlargement of the thymus. Other symptoms include loss of appetite, weight loss, weakness, depression, and coughing. It can also masquerade as a chronic disease such as an upper respiratory infection or gastrointestinal disease. In older ferrets, lymphoma is usually chronic and can exhibit no symptoms for years. Symptoms seen are the same as in young ferrets, plus splenomegaly, abdominal masses, and peripheral lymph node enlargement.

Diagnosis is through biopsy and x-rays. There may also be an increased lymphocyte count. Treatment includes surgery for solitary tumors, splenectomy (when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide. Doxorubicin is used in some cases. Chemotherapy in relatively healthy ferrets is tolerated very well, but possible side effects include loss of appetite, depression, weakness, vomiting, and loss of whiskers. The white blood cell count must be monitored. Prednisone used alone can work very well for weeks to months, but it may cause resistance to other chemotherapy agents. Alternative treatments include vitamin C and Pau d'Arco (a bark extract).

The prognosis for lymphoma in ferrets depends on their health and the location of the cancer. Lymphoma in the mediastinum, spleen, skin, and peripheral lymph nodes has the best prognosis, while lymphoma in the intestine, liver, abdominal lymph nodes, and bone marrow has the worst.

CHOP frequently induces remission initially, but most patients relapse and die within two years. Autologous bone marrow transplantation is currently being investigated in the treatment of hepatosplenic lymphoma. Allogeneic bone marrow transplant has been proven to attain remission for over five years and possibly cure hepatosplenic lymphoma.

Thyroid lymphoma shows a diagnostic and therapeutic challenge in many cases, because some manifestation patterns are similar to anaplastic thyroid cancer (ATC). Performance of fine-needle aspiration (FNA) has helped to distinguish these between two entities preoperatively.

The prognosis is generally poor. The "RS score" (Richter syndrome score), which is an estimate of the patient's prognosis, is based on the patient's performance status, LDH, platelet count, the size of the lymphoma tumors, and the number of prior therapies already received. Overall, the median survival is between five and eight months. Untreated, RS is invariably fatal.

The Hodgkin's lymphoma variant of Richter's carries a better prognosis than the predominant diffuse large B-cell lymphoma type, but a worse prognosis than a "de novo" case of Hodgkin's.

The majority of gastric lymphomas are non-Hodgkin's lymphoma of B-cell origin. These tumors may range from well-differentiated, superficial involvements (MALT) to high-grade, large-cell lymphomas. Sometimes, it's hard to differentiate poorly differentiated high grade B-cell gastric lymphoma from gastric adenocarcinoma clinically or radiologically, yet histopathology with immunohistochemistry is recommended to stain specific markers on the malignant cell that favor the diagnosis of lymphoma. Immunohistochemistry stains specific clusters of differentiation that are present on B-cells like CD20. Cytokeratin is also a surface marker that is presented on epithelial cells, is stained histochemically and favors the diagnosis of epithelial tumors like adenocarcinoma.

Differentiating poor gastric lymphoma from adenocarcinoma is essential because the prognosis and modalities of treatment differ significantly.

Other lymphomas involving the stomach include mantle cell lymphoma and T-cell lymphomas which may be associated with enteropathy; the latter usually occur in the small bowel but have been reported in the stomach.

According to the Peripheral T-Cell Lymphoma Project, median overall survival is ten months, while median failure-free survival is only six months . The peripheral index for T-cell lymphoma is useful in defining prognosis for enteropathy-associated T-cell lymphoma. Among the most influential prognostic factors is bulky disease, defined by a tumor mass greater than 5 cm.

Autologous stem cell transplantation is feasible for selected patients with enteropathy-associated T-cell lymphoma and can yield durable disease control in a significant proportion of these patients. One study found a trend for better survival in patients transplanted in first complete or partial remission at four years (66% vs. 36%; P = .062).

Castleman disease is diagnosed when a lymph node biopsy reveals regression of germinal centers, abnormal vascularity, and a range of hyaline vascular changes and/or polytypic plasma cell proliferation. These features can also be seen in other disorders involving excessive cytokine release, so they must be excluded before a Castleman disease diagnosis should be made.

It is essential for the biopsy sample to be tested for HHV-8 with latent associated nuclear antigen (LANA) by immunohistochemistry or PCR for HHV-8 in the blood.

These lymphomas are difficult to differentiate from gastric adenocarcinoma. The lesions are usually ulcers with a ragged, thickened mucosal pattern on contrast radiographs.

The diagnosis is typically made by biopsy at the time of endoscopy. Several endoscopic findings have been reported, including solitary ulcers, thickened gastric folds, mass lesions and nodules. As there may be infiltration of the submucosa, larger biopsy forceps, endoscopic ultrasound guided biopsy, endoscopic submucosal resection, or laparotomy may be required to obtain tissue.

Imaging investigations including CT scans or endoscopic ultrasound are useful to stage disease. Hematological parameters are usually checked to assist with staging and to exclude concomitant leukemia. An elevated LDH level may be suggestive of lymphoma.

There are three sub-types of Castleman disease.

- Unicentric Castleman disease

- HHV-8-associated multicentric Castleman disease

- HHV-8-negative multicentric Castleman disease

T-PLL is an extremely rare aggressive disease, and patients are not expected to live normal lifespans. Before the recent introduction of better treatments, such as alemtuzumab, the median survival time was 7.5 months after diagnosis. More recently, some patients have survived five years and more, although the median survival is still low.

There are numerous kinds of lymphomas involving B cells. The most commonly used classification system is the WHO classification, a convergence of more than one, older classification systems.