Because many organs can be affected by myeloma, the symptoms and signs vary greatly. A mnemonic sometimes used to remember some of the common symptoms of multiple myeloma is CRAB: C = calcium (elevated), R = renal failure, A = anemia, B = bone lesions. Myeloma has many other possible symptoms, including opportunistic infections (e.g., pneumonia) and weight loss. CRAB symptoms and proliferation of monoclonal plasma cells in the bone marrow are part of the diagnostic criteria of multiple myeloma.

Some symptoms (e.g., weakness, confusion, and fatigue) may be due to anemia or hypercalcemia. Headache, visual changes, and retinopathy may be the result of hyperviscosity of the blood depending on the properties of the paraprotein. Finally, radicular pain, loss of bowel or bladder control (due to involvement of spinal cord leading to cord compression) or carpal tunnel syndrome, and other neuropathies (due to infiltration of peripheral nerves by amyloid) may occur. It may give rise to paraplegia in late-presenting cases.

When the disease is well-controlled, neurological symptoms may result from current treatments, some of which may cause peripheral neuropathy, manifesting itself as numbness or pain in the hands, feet, and lower legs.

Signs and symptoms of WM include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.

For SPB the most common presenting symptom is that of pain in the affected bone. Back pain and other consequences of the bone lesion may occur such as spinal cord compression or pathological fracture. Around 85% of extramedullary plasmacytoma presents within the upper respiratory tract mucosa, causing possible symptoms such as epistaxis, rhinorrhoea and nasal obstruction. In some tissues it may be found as a palpable mass.

There can be some ambiguity when using the word. "Plasmacytoma" is sometimes equated with "plasma cell dyscrasia" or "solitary myeloma". It is often used as part of the phrase "solitary plasmacytoma". or as part of the phrase "extramedullary plasmacytoma". In this context, "extramedullary" means outside of the bone marrow.

People with monoclonal gammopathy generally do not experience signs or symptoms. Some people may experience a rash or nerve problems, such as numbness or tingling. Severe renal disease has also been found in a subset of those with monoclonal gammopathy. MGUS is usually detected by chance when the patient has a blood test for another condition or as part of standard screening.

The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing an hypercalcemic crisis, i.e. an potentially life-threatening episode of high ionic calcium (Ca) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.

Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.

Monoclonal gammopathy of undetermined significance (MGUS, "unknown" or "uncertain" may be substituted for "undetermined"), formerly benign monoclonal gammopathy, is a condition in which an abnormal immunoglobin protein (known as a paraprotein) is found in the blood during standard laboratory blood tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibody are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it has no symptoms or major problems. However, multiple myeloma develops at the rate of about 1.5% a year, so doctors recommend monitoring it yearly.

The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.

Waldenström's macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is a type of cancer affecting two types of B cells, lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. WM is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. WM is an "indolent lymphoma" (i.e., one that tends to grow and spread slowly) and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. WM is commonly classified as a form of plasma cell dyscrasia. Similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma, WM is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance (i.e. IgM MGUS) and smoldering Waldenström's macroglobulinemia. The WM spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.

WM is a rare disease, with only about 1,500 cases per year in the United States. While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and when treatment is required, may experience years of symptom-free remission.

Causes of paraproteinemia include the following:

- Leukemias and lymphomas of various types, but usually B-cell Non-Hodgkin lymphomas with a plasma cell component.

- Myeloma

- Plasmacytoma

- Lymphoplasmacytic lymphoma

- Idiopathic (no discernible cause): some of these will be revealed as leukemias or lymphomas over the years.

- Monoclonal gammopathy of undetermined significance

- Primary AL amyloidosis (light chains only)

Tumors of the hematopoietic and lymphoid tissues or haematopoietic and lymphoid malignancies are tumors that affect the blood, bone marrow, lymph, and lymphatic system. As those elements are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.

While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of haematological malignancies.

Haematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "Haematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all haematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.

Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.

A subgroup of them are more severe and are known as haematological malignancies (American spelling hematological malignancies) or blood cancer. They may also be referred to as liquid tumors.

Paraproteinemia, also known as monoclonal gammopathy, is the presence of excessive amounts of paraprotein or single monoclonal gammaglobulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia.

Monoclonal B-cell lymphocytosis (MBL) is a condition that resembles chronic lymphocytic leukemia (CLL), but does not meet the criteria for CLL, and does not require treatment. However, CLL requiring treatment develops at the rate of 1.1% per year.

The definition of CLL includes >5,000 CLL-phenotype B-cell lymphocytes per cubic millimeter. Patients with <5,000 (but not 0) CLL-phenotype B-cell lymphocytes per mm³, and no symptoms of CLL, are diagnosed with MBL.

The term monoclonal means that all the B cells are derived from a single cell.

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

Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:

In 2008, the World Health Organization listed these diagnoses as types of MPD:

- Chronic myelogenous leukemia (BCR-ABL1–positive)

- Chronic neutrophilic leukemia

- Polycythemia vera

- Primary myelofibrosis

- Essential thrombocythemia

- Chronic eosinophilic leukemia (not otherwise specified)

- Mastocytosis

Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's own T-cells.

Human T cell leukemia/lymphotropic virus type 1 (HTLV-1) is believed to be the cause of it, in addition to several other diseases.

The myeloproliferative neoplasms (MPNs), previously myeloproliferative diseases (MPDs), are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than these conditions. The concept of myeloproliferative disease was first proposed in 1951 by the hematologist William Dameshek. In the most recent World Health Organization classification of hematologic malignancies, this group of diseases was renamed from "myeloproliferative diseases" to "myeloproliferative neoplasms". This reflects the underlying clonal genetic changes that are a salient feature of this group of disease.

The increased numbers of blood cells may not cause any symptoms, but a number of medical problems or symptoms may occur. The risk of thrombosis is increased in some types of MPN.

For the analysis of a suspected "hematological malignancy", a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.

ATL is usually a highly aggressive non-Hodgkin's lymphoma with no characteristic histologic appearance except for a diffuse pattern and a mature T-cell phenotype. Circulating lymphocytes with an irregular nuclear contour (leukemic cells) are frequently seen. Several lines of evidence suggest that HTLV-1 causes ATL. This evidence includes the frequent isolation of HTLV-1 from patients with this disease and the detection of HTLV-1 proviral genome in ATL leukemic cells. ATL is frequently accompanied by visceral involvement, hypercalcemia, skin lesions, and lytic bone lesions. Bone invasion and osteolysis, features of bone metastases, commonly occur in the setting of advanced solid tumors, such as breast, prostate, and lung cancers, but are less common in hematologic malignancies. However, patients with HTLV-1–induced ATL and multiple myeloma are predisposed to the development of tumor-induced osteolysis and hypercalcemia. One of the striking features of ATL and multiple myeloma induced bone disease is that the bone lesions are predominantly osteolytic with little associated osteoblastic activity. In patients with ATL, elevated serum levels of IL-1, TGFβ, PTHrP, macrophage inflammatory protein (MIP-1α), and receptor activator of nuclear factor-κB ligand (RANKL) have been associated with hypercalcemia. Immunodeficient mice that received implants with leukemic cells from patients with ATL or with HTLV-1–infected lymphocytes developed hypercalcemia and elevated serum levels of PTHrP. Most patients die within one year of diagnosis.

Infection with HTLV-1, like infection with other retroviruses, probably occurs for life and can be inferred when antibody against HTLV-1 is detected in the serum.

Lymphoma is a group of blood cancers that develop from lymphocytes (a type of white blood cell). The name often refers to just the cancerous versions rather than all such tumors. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

There are dozens of subtypes of lymphomas. The two main categories of lymphomas are Hodgkin's lymphomas (HL) and the non-Hodgkin lymphomas (NHL). The World Health Organization (WHO) includes two other categories as types of lymphoma: multiple myeloma and immunoproliferative diseases. About 90% of lymphomas are non-Hodgkin lymphomas. Lymphomas and leukemias are a part of the broader group of tumors of the hematopoietic and lymphoid tissues.

Risk factors for Hodgkin lymphoma include infection with Epstein–Barr virus and a history of the disease in the family. Risk factors for common types of non-Hodgkin lymphomas include autoimmune diseases, HIV/AIDS, infection with human T-lymphotropic virus, immunosuppressant medications, and some pesticides. Eating large amounts of red meat and tobacco smoking may also increase the risk. Diagnosis, if enlarged lymph nodes are present, is usually by lymph node biopsy. Blood, urine, and bone marrow testing may also be useful in the diagnosis. Medical imaging may then be done to determine if and where the cancer has spread. Lymphoma most often spreads to the lungs, liver, and brain.

Treatment may involve one or more of the following: chemotherapy, radiation therapy, targeted therapy, and surgery. In some non-Hodgkin lymphomas, an increased amount of protein produced by the lymphoma cells causes the blood to become so thick that plasmapheresis is performed to remove the protein. Watchful waiting may be appropriate for certain types. The outcome depends on the subtype with some being curable and treatment prolonging survival in most. The five-year survival rate in the United States for all Hodgkin lymphoma subtypes is 85%, while that for non-Hodgkin lymphomas is 69%. Worldwide, lymphomas developed in 566,000 people in 2012 and caused 305,000 deaths. They make up 3–4% of all cancers, making them as a group the seventh-most common form. In children, they are the third-most common cancer. They occur more often in the developed world than the developing world.

The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.

AL amyloidosis can occur spontaneously. It is, however, often associated with other blood disorders, such as multiple myeloma and Waldenström's macroglobulinemia. About 10% to 15% of patients with multiple myeloma may develop overt AL amyloidosis.

Using flow cytometry, monoclonal cells with cell surface markers similar to those in CLL can be detected in some healthy adults, who do not meet the criteria for CLL (i.e., >5,000 CLL-type lymphocytes per mm³). If the diagnosis of CLL is based on the B cell count rather than the total lymphocyte count (which includes both B and T cells), many patients formerly diagnosed with Rai Stage 0 CLL would instead be classified as having MBL.

Molecular techniques can detect monoclonal B cell levels as low as 3-5 B cells/microliter (comparable to the amount of stem cells in peripheral blood).

The term "monoclonal B-cell lymphocytosis" was proposed by a consensus committee in 2005 to indicate a monoclonal B cell population in a person with fewer than 5,000 B lymphocytes per microliter (or 5.0 x 10 B lymphocytes/L), no enlarged lymph nodes or enlarged liver and/or spleen or other indications of a lymphoproliferative disorder.

AL amyloidosis can affect a wide range of organs, and consequently present with a range of symptoms. The kidneys are the most commonly affected organ in AL amyloidosis. Symptoms of kidney disease and renal failure can include fluid retention, swelling, and shortness of breath.

In addition to kidneys, AL amyloidosis may affect the heart, peripheral nervous system, gastrointestinal tract, blood, lungs and skin. Heart complications, which affect more than a third of AL patients, include heart failure and irregular heart beat. Other symptoms can include stroke, gastrointestinal disorders, enlarged liver, diminished spleen function, diminished function of the adrenal and other endocrine glands, skin color change or growths, lung problems, bleeding and bruising problems, fatigue and weight loss.