The clinical presentation varies according to the type of ALCL. Two of the ALCL subtypes are systemic lymphomas, in that they usually present with enlarged lymph nodes in multiple regions of the body, or with tumors outside the lymph nodes (extranodal) such as bone, intestine, muscle, liver, or spleen. These 2 subtypes usually associate with weight loss, fevers and night sweats, and can be lethal if left untreated without chemotherapy. The third type of ALCL is so-called cutaneous ALCL, and is a tumor that presents in the skin as ulcers that may persist, or occasionally may involute spontaneously, and commonly recur. This type of ALCL usually manifests in different regions of the body and may extend to regional lymph nodes, i.e., an axillary lymph node if the ALCL presents in the arm.

A rare subtype of ALCL has been identified in a few women who have silicone breast implants (protheses) as a result of breast reconstruction after a diagnosis of breast cancer. The tumor initially manifests with swelling of the breast due to fluid accumulation around the implant. The disease may progress to invade the tissue surrounding the capsule, and if left untreated may progress to the axillary lymph nodes.

It typically presents at a late stage and is often associated with systemic symptoms ("B symptoms").

The median age of diagnosis is approximately fourth and fifth decades. The disease often arises in the oral cavity, particularly in HIV disease, but other sites include nasal cavity, gastrointestinal tract, skin, bone soft tissue, and lung. There is usually immunodeficiency, such as HIV, organ transplants, autoimmune diseases

Like Burkitt's lymphoma, the morphology has a "starry sky". However, the immunophenotype resembles plasma cells: CD45-, CD20-, CD79a+/-, PAX5-, CD38+, CD38+ and MUM1+. Ki67 is over 90%. EBV is positive in 75%; HHV-8 is negative.

Anaplastic large-cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma involving aberrant T cells or null lymphocytes. It is described in detail in the "Classification of Tumours of the Haematopoietic and Lymphoid Tissues" edited by experts of the World Health Organisation (WHO). The term anaplastic large cell lymphoma (ALCL) encompasses at least 4 different clinical entities, all sharing the same name, and histologically have also in common the presence of large pleomorphic cells that express CD30 and T-cell markers. Two types of ALCL present as systemic disease and are considered as aggressive lymphomas, while two types present as localized disease and may progress locally.

Its name derives from anaplasia and large-cell lymphoma.

Plasmablastic lymphoma is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is CD20 negative, and has an immunophenotype that resembles plasma cells. In formal use, lymphomas with plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease and extracavitary HHV–8-positive lymphoma are not part of this category, although sometimes the literature has confused this point.

Diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of diseases, many of which cannot be separated from one another by well-defined and widely accepted criteria. The World Health Organization (WHO) classification system defines more than a dozen subtypes, each of which can be differentiated based on the location of the tumor, the presence of other cells within the tumor (such as T cells), and whether the patient has certain other illnesses related to DLBCL. One of these well-defined groupings of particular note is "primary mediastinal (thymic) large B cell lymphoma", which arises within the thymus or mediastinal lymph nodes.

In some cases, a tumor may share many features with both DLBCL and Burkitt's lymphoma. In these situations, the tumor is classified as simply “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma”. A similar situation can arise between DLBCL and Hodgkin's lymphoma; the tumor is then classified as “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Hodgkin’s lymphoma”.

When a case of DLBCL does not conform to any of these subtypes, and is also not considered unclassifiable, then it is classified as “diffuse large B-cell lymphoma, not otherwise specified” (DLBCL, NOS). The majority of DLBCL cases fall into this category. Much research has been devoted to separating this still-heterogeneous group; such distinctions are usually made along lines of cellular morphology, gene expression, and immunohistochemical properties.

Currently, Burkitt lymphoma can be divided into three main clinical variants: the endemic, the sporadic, and the immunodeficiency-associated variants.

- The endemic variant (also called "African variant") most commonly occurs in children living in malaria endemic regions of the world (e.g., equatorial Africa, Brazil, and Papua New Guinea). Epstein-Barr virus (EBV) infection is found in nearly all patients. Chronic malaria is believed to reduce resistance to EBV, allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney, or breast.

- The sporadic type of Burkitt lymphoma (also known as "non-African") is the most common variant found in places where malaria is not holoendemic. The tumor cells have a similar appearance to the cancer cells of classical endemic Burkitt lymphoma. Sporadic lymphomas are rarely associated with the Epstein–Barr virus. Non-Hodgkin lymphoma, which includes Burkitt's, accounts for 30–50% of childhood lymphoma. The jaw is less commonly involved, compared to the endemic variant. The ileocecal region is the common site of involvement.

- Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.

By morphology (i.e., microscopic appearance) or immunophenotype, it is almost impossible to differentiate these three clinical variants. Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific.

Diffuse large B-cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the USA and the UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age, though it can also occur in children and young adults in rare cases. DLBCL is an aggressive tumor which can arise in virtually any part of the body, and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with B symptoms—fever, weight loss, and night sweats.

The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma or leukemia. An underlying immunodeficiency is a significant risk factor. Infection with Epstein–Barr virus has also been found to contribute to the development of some subgroups of DLBCL.

Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis. Several subtypes of DLBCL have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is chemotherapy, often in combination with an antibody targeted at the tumor cells. Through these treatments, more than half of patients with DLBCL can be cured, and the overall five-year survival rate for older adults is around 58%.

A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss.Other symptoms include

- diplopia

- dysphagia

- vertigo

- monocular vision loss

- progressive dementia or stupor in patients with a nonfocal neurologic exam and minimal abnormalities on MRI (more common in AIDS patients)

- facial hypoesthesia

The symptoms of AIDS-related lymphoma can include: weight loss, fever, and night sweats.

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1958 while working in equatorial Africa.

Primary mediastinal (thymic) large B-cell lymphoma, also called primary mediastinal large B-cell lymphoma (PMLBCL) and mediastinal large B-cell lymphoma, is a distinct type of diffuse large B-cell lymphoma involving the mediastinum, recognized in the WHO 2008 classification.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.

Lymphoma may present with certain nonspecific symptoms; if the symptoms are persistent, an evaluation to determine their cause, including possible lymphoma, should be undertaken.

- Lymphadenopathy or swelling of lymph nodes, is the primary presentation in lymphoma.

- B symptoms (systemic symptoms) – can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. They consist of:

- Fever

- Night sweats

- Weight loss

- Other symptoms:

- Loss of appetite or anorexia

- Fatigue

- Respiratory distress or dyspnea

- Itching

Intravascular large B-cell lymphoma (ILBCL), also referred to as angiotropic large-cell lymphoma, angiotropic large-cell lymphoma, intralymphatic lymphomatosis, intravascular lymphomatosis, and, less specifically, intravascular lymphoma and malignant angioendotheliomatosis is a rare form of lymphoma.

Mixed-cell lymphomas are lymphomas that have both large cells and small cells in them. This nomenclature is derived from an older system of pathology, before technological advances allowed much more precise descriptions of the affected cancerous cells.

In MeSH, the phrase "mixed-cell lymphoma" is currently classified under non-Hodgkin lymphoma.

Follicular large-cell lymphoma is a rare type of non-Hodgkin lymphoma (cancer of the lymphatic system) with large cells that look cleaved (split) or non-cleaved under the microscope. It is an indolent (slow-growing) type of lymphoma.

In MeSH, it is currently classified under follicular lymphoma.

One classification system for lymphomas divides the diseases according to the size of the white blood cells that has turned cancerous. The large-cell lymphomas have large cells. A large cell, in this context, has a diameter of 17 to 20 µm. Other groups of lymphomas in this system are the small-cell lymphomas and mixed-cell lymphomas.

The cancer is classified into low and high grade types. Classification is also based on location. The four location types are multicentric, mediastinal, gastrointestinal, and extranodal (involving the kidney, central nervous system, skin, heart, or eye). Multicentric lymphoma, the most common type (by greater than 80 percent), is found in the lymph nodes, with or without involvement in the liver, spleen, or bone marrow. Mediastinal lymphoma occurs in the lymph nodes in the thorax and possibly the thymus. Gastrointestinal lymphoma occurs as either a solitary tumor or diffuse invasion of the stomach or intestines, with or without involvement in the surrounding lymph nodes, liver or spleen. Classification is further based on involvement of B-lymphocytes or T-lymphocytes. Approximately 70 percent are B-cell lymphoma. Cutaneous lymphoma can be classified as epitheliotropic (closely conforming to the epidermis) or non-epitheliotropic. The epitheliotropic form is typically of T-cell origin and is also called mycosis fungoides. The non-epitheliotropic form is typically of B-cell origin.

At diagnosis, patients typically are in their 60s and present to their physician with advanced disease. About half have either fever, night sweats, or unexplained weight loss (over 10% of body weight). Enlarged lymph nodes (for example, a "bump" on the neck, armpits or groin) or splenomegaly are usually present. Bone marrow, liver and GI tract involvement occurs relatively early in the course of the disease.

General signs and symptoms include depression, fever, weight loss, loss of appetite, loss of hair or fur and vomiting. Lymphoma is the most common cancerous cause of hypercalcemia (high blood calcium levels) in dogs. It can lead to the above signs and symptoms plus increased water drinking, increased urination, and cardiac arrhythmias. Hypercalcemia in these cases is caused by secretion of parathyroid hormone-related protein.

Multicentric lymphoma presents as painless enlargement of the peripheral lymph nodes. This is seen in areas such as under the jaw, the armpits, the groin, and behind the knees. Enlargement of the liver and spleen causes the abdomen to distend. Mediastinal lymphoma can cause fluid to collect around the lungs, leading to coughing and difficulty breathing. Hypercalcemia is most commonly associated with this type.

Gastrointestinal lymphoma causes vomiting, diarrhea, and melena (digested blood in the stool). Low serum albumin levels and hypercalcemia can also occur.

Lymphoma of the skin is an uncommon occurrence. The epitheliotropic form typically appears as itchy inflammation of the skin progressing to nodules and plaques.

The non-epitheliotropic form can have a wide variety of appearances, from a single lump to large areas of bruised, ulcerated, hairless skin. The epitheliotropic form must be differentiated from similar appearing conditions such as pemphigus vulgaris, bullous pemphigoid, and lupus erythematosus.

Signs for lymphoma in other sites depend on the location. Central nervous system involvement can cause seizures or paralysis. Eye involvement, seen in 20 to 25 percent of cases, can lead to glaucoma, uveitis, bleeding within the eye, retinal detachment, and blindness. Lymphoma in the bone marrow causes anemia, low platelet count, and low white blood cell count.

The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals.

B-cell lymphomas include both Hodgkin's lymphomas and most non-Hodgkin lymphomas. They are typically divided into low and high grade, typically corresponding to indolent (slow-growing) lymphomas and aggressive lymphomas, respectively. As a generalisation, indolent lymphomas respond to treatment and are kept under control (in remission) with long-term survival of many years, but are not cured. Aggressive lymphomas usually require intensive treatments, with some having a good prospect for a permanent cure.

Prognosis and treatment depends on the specific type of lymphoma as well as the stage and grade. Treatment includes radiation and chemotherapy. Early-stage indolent B-cell lymphomas can often be treated with radiation alone, with long-term non-recurrence. Early-stage aggressive disease is treated with chemotherapy and often radiation, with a 70-90% cure rate. Late-stage indolent lymphomas are sometimes left untreated and monitored until they progress. Late-stage aggressive disease is treated with chemotherapy, with cure rates of over 70%.

A primary central nervous system lymphoma (PCNSL), also known as microglioma and primary brain lymphoma, is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). PCNSLs represent around 20% of all cases of lymphomas in HIV infections (other types are Burkitt's lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/uL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50's and 60's. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.

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.

Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S.

MCL is a subtype of B-cell lymphoma, due to CD5 positive antigen-naive pregerminal center B-cell within the mantle zone that surrounds normal germinal center follicles. MCL cells generally over-express cyclin D1 due to a t(11:14) chromosomal translocation in the DNA. Specifically, the translocation is at t(11;14)(q13;q32).

Lymphomas in the strict sense are any neoplasms of the lymphatic tissues ("" + "") . The main classes are malignant neoplasms (that is, cancers) of the lymphocytes, a type of white blood cell that belongs to both the lymph and the blood and pervades both. Thus, lymphomas and leukemias are both tumors of the hematopoietic and lymphoid tissues, and as lymphoproliferative disorders, lymphomas and lymphoid leukemias are closely related, to the point that some of them are unitary disease entities that can be called by either name (for example, adult T-cell leukemia/lymphoma).

Several classification systems have existed for lymphoma, which use histological and other findings to divide lymphoma into different categories. The classification of a lymphoma can affect treatment and prognosis. Classification systems generally classify lymphoma according to:

- Whether or not it is a Hodgkin lymphoma

- Whether the cell that is replicating is a T cell or B cell

- The site from which the cell arises

Lymphoma can also spread to the central nervous system, often around the brain in the meninges, known as lymphomatous meningitis (LM).