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

Patients with Hodgkin's lymphoma may present with the following symptoms:

- Lymph nodes: the most common symptom of Hodgkin's is the painless enlargement of one or more lymph nodes, or lymphadenopathy. The nodes may also feel rubbery and swollen when examined. The nodes of the neck and shoulders (cervical and supraclavicular) are most frequently involved (80–90% of the time, on average). The lymph nodes of the chest are often affected, and these may be noticed on a chest radiograph.

- Itchy skin

- Night sweats

- Unexplained weight loss

- Splenomegaly: enlargement of the spleen occurs in about 30% of people with Hodgkin's lymphoma. The enlargement, however, is seldom massive, and the size of the spleen may fluctuate during the course of treatment.

- Hepatomegaly: enlargement of the liver, due to liver involvement, is present in about 5% of cases.

- Hepatosplenomegaly: the enlargement of both the liver and spleen caused by the same disease.

- Pain following alcohol consumption: classically, involved nodes are painful after alcohol consumption, though this phenomenon is very uncommon, occurring in only two to three percent of people with Hodgkin's lymphoma, thus having a low sensitivity. On the other hand, its positive predictive value is high enough for it to be regarded as a pathognomonic sign of Hodgkin lymphoma. The pain typically has an onset within minutes after ingesting alcohol, and is usually felt as coming from the vicinity where there is an involved lymph node. The pain has been described as either sharp and stabbing or dull and aching.

- Back pain: nonspecific back pain (pain that cannot be localised or its cause determined by examination or scanning techniques) has been reported in some cases of Hodgkin's lymphoma. The lower back is most often affected.

- Red-coloured patches on the skin, easy bleeding and petechiae due to low platelet count (as a result of bone marrow infiltration, increased trapping in the spleen etc.—i.e. decreased production, increased removal)

- Systemic symptoms: about one-third of patients with Hodgkin's disease may also present with systemic symptoms, including low-grade fever; night sweats; unexplained weight loss of at least 10% of the patient's total body mass in six months or less, itchy skin (pruritus) due to increased levels of eosinophils in the bloodstream; or fatigue (lassitude). Systemic symptoms such as fever, night sweats, and weight loss are known as B symptoms; thus, presence of fever, weight loss, and night sweats indicate that the patient's stage is, for example, 2B instead of 2A.

- Cyclical fever: patients may also present with a cyclical high-grade fever known as the Pel-Ebstein fever, or more simply "P-E fever". However, there is debate as to whether the P-E fever truly exists.

- Nephrotic syndrome can occur in individuals with Hodgkin's lymphoma and is most commonly caused by minimal change disease.

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

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).

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%.

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.

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.

Hodgkin's lymphoma (HL) is a type of lymphoma, which is generally believed to result from white blood cells of the lymphocyte kind. Symptoms may include fever, night sweats, and weight loss. Often there will be non-painful enlarged lymph nodes in the neck, under the arm, or in the groin. Those affected may feel tired or be itchy.

About half of cases of Hodgkin's lymphoma are due to Epstein–Barr virus (EBV). Other risk factors include a family history of the condition and having HIV/AIDS. There are two major types of Hodgkin lymphoma: classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Diagnosis is by finding Hodgkin's cells such as multinucleated Reed–Sternberg cells (RS cells) in lymph nodes.

Hodgkin lymphoma may be treated with chemotherapy, radiation therapy, and stem cell transplant. The choice of treatment often depends on how advanced the cancer has become and whether or not it has favorable features. In early disease, a cure is often possible. The percentage of people who survive five years in the United States is 86%. For those under the age of 20, rates of survival are 97%. Radiation and some chemotherapy drugs, however, increase the risk of other cancers, heart disease, or lung disease over the subsequent decades.

In 2015 about 574,000 people had Hodgkin's lymphoma, and 23,900 died. In the United States, 0.2% of people are affected at some point in their life. The most common age of diagnosis is between 20 and 40 years old. It was named after the English physician Thomas Hodgkin, who first described the condition in 1832.

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.

Non-Hodgkin's lymphoma (NHL) is present in about 1%–3% of HIV seropositive people at the time of the initial diagnosis of HIV. However, it is believed that such patients have been seropositive for a prolonged period, but have simply not had their infections recognized previously. This is so because immunodysregulation must exist for an extended interval of time, in order for a lymphoproliferative process to evolve in that context.

The spleen and liver are always involved, with bone marrow involvement frequently present. Nodal involvement is exceedingly rare.

The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegaly.

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").

Symptoms of Richter’s transformation in a CLL patient include fever (without infection), an elevated serum levels of lactate dehydrogenase, and rapidly enlarging lymph nodes. While about 8% of all CLL patients will have elevated levels of serum lactate dehydrogenase (LDH), more than 50% of CLL patients with Richter's transformation will have elevated LDH levels.

Richter's can appear suddenly, even in patients who were in remission.

There are two main types of intraocular lymphomas: primary central nervous system involvement (PCNSL) and primary central nervous system with ocular involvement (PCNSLO). The difference between PCNSL and PCNSLO is that PNSCL involves the central nervous system, while PCNSLO does not. 56-86% of orbital lymphomas are classified PCNSL and 15-25% are classified PCNSLO.

PCNSLO is common in people who are severely immunosuppressed.

Symptoms of this form of ocular lymphoma include painless decreased vision, sensitivity to light, a red eye, and floaters. Diagnosis is difficult due to its gradual onset and the fact that the symptoms are the same as other diseases.

PCNSLO is usually bilateral, but sometimes grows unevenly. Like other metastatic tumors of the eye, it is usually confined to the choroid.

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.

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).

Follicular lymphoma is a type of blood cancer. It is the most common of the indolent (slow-growing) non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. It is positive for the B-cell markers CD10, CD19, CD22, and usually CD20, but almost always negative for CD5.

There are several synonymous and obsolete terms for this disease, such as CB/CC lymphoma (Centroblastic and Centrocytic lymphoma), nodular lymphoma and Brill-Symmers Disease.

Primary visible signs of ocular lymphoma include proptosis and a visible mass in the eye. Symptoms are due to mass effect.

According to the WHO criteria, the disease is morphologically graded into:

- grade 1 (<5 centroblasts per high-power field (hpf))

- grade 2 (6–15 centroblasts/hpf)

- grade 3 (>15 centroblasts/hpf).

Grade 3 is further subdivided into:

- grade 3A (centrocytes still present)

- grade 3B (the follicles consist almost entirely of centroblasts)

The WHO 2008 update classifies grades 1 and 2 now as low grade follicular lymphoma, grade 3A as high grade follicular lymphoma, and grade 3B as Diffuse Large B Cell Lymphoma (DLBCL).

Ann Arbor staging is used to classify tumors and symptoms. Stage IV disease is very rare.

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.

Diagnosis usually occurs at an early stage of disease progression.

"MALT lymphoma" is an often multifocal disease in the organ of origin and is frequently macroscopically indistinguishable from other disease processes in the GI tract. Endoscopy is key to diagnosing "MALT lymphoma", with multiple biopsies of the visible lesions required, as well as samples of macroscopically normal tissue, termed gastric mapping. Histologically, there is expansion of the marginal zone compartment with development of sheets of neoplastic small lymphoid cells. The morphology of the neoplastic cells is variable with small mature lymphocytes, cells resembling centrocytes (centrocyte like cells), or marginal zone/monocytoid B cells. Plasmacytoid or plasmacytic differentiation is frequent. Lymphoid follicles are ubiquitous to "MALT lymphoma" but may be indistinct as they are often overrun or colonized by the neoplastic cells. Large transformed B cells are present scattered among the small cell population. If these large cells are present in clusters or sheets, a diagnosis of associated large B-cell lymphoma should be considered. A characteristic feature of MALT lymphoma is the presence of neoplastic cells within epithelial structures with associated destruction of the glandular architecture to form lymphoepithelial lesions.

"MALT lymphoma" may be difficult to distinguish from reactive infiltrates, and in some cases, multiple endoscopies are required before a confident diagnosis is reached. The Wotherspoon score, which grades the presence of histological features associated with "MALT lymphoma", is useful in expressing confidence in diagnosis at presentation.

Immunohistochemistry can be used to help distinguish "MALT lymphoma" from other small B-cell NHLs. B-cell-associated antigens such as CD19, CD20, CD22, and CD79a are usually expressed. In contrast to small lymphocytic lymphoma and MCL, staining for CD5 is usually negative, and these lymphomas can be further distinguished with CD23 (positive in small lymphocytic lymphoma) and CyclinD1 (positive in MCL).

Diffuse large B-cell lymphoma is the most common of the large-cell lymphomas. MeSH now classifies the phrase "large-cell lymphoma" under "Diffuse large B cell lymphoma".

Many other B-cell lymphomas feature large cells:

- Angiocentric lymphoma

- Burkitt’s lymphoma

- Follicular large-cell lymphoma

- Immunoblastic lymphoma

- Intravascular large-cell lymphoma

- Primary mediastinal B-cell lymphoma

- T-cell–rich B-cell lymphoma

- Primary splenic lymphoma (rare)

- Primary central nervous system lymphomas, which are often diffuse large-B-cell lymphomas

Activated B-Cell Diffuse Large B-Cell Lymphoma, or ABC-DLBCL, is believed to be caused by aberrant activation of a critical intracellular pathway.

This intracellular signaling pathway involved in B-cell activation and proliferation stays constantly activated, driving lymphocytes to proliferate continuously.

The inhibition of this pathway can be induced by a drug known as NEMO Binding Domain, or NBD, a peptide causing increased cell death of malignant lymphocytes.