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

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure.

In hairy cell leukemia, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count. Leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when he or she has not eaten much.

Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers of one or more kinds of normal blood cells, or after unexplained bruises or recurrent infections in an otherwise apparently healthy patient.

Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect. It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue.

Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen. Cholesterol levels return to more normal values with successful treatment of HCL.

This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.

Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.

The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.

One of the most common signs of CMML is splenomegaly, found in approximately half of cases. Other less frequent signs and symptoms consist of anaemia, fever, weight loss, night sweats, infection, bleeding, synovitis, lymphadenopathy, skin rashes, pleural effusion, pericardial effusion and peritoneal effusion.

Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.

It is also called "aggressive NK-cell lymphoma".

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.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.

Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs.

Clinically, clonal eosinophilia resembles various types of chronic or acute leukemias, lymphomas, or myeloproliferative hematological malignancies. However, many of the clonal hypereosinophilias are distinguished from these other hematological malignancies by the genetic mutations which underlie their development and, more importantly, by their susceptibility to specific treatment regiments. That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs.

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.

Chronic myelomonocytic leukaemia (CMML) is a type of leukaemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell.

CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative disorder (MPD); a disorder characterised by the overproduction of blood cells. For this reason CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organisation (WHO) states that the blood monocyte count must be >1x10/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be <20% and dysplasia of at least one lineage of myeloid blood cell should be present.

Azacitidine is a drug used to treat CMML and is approved by the Food and Drug Administration (FDA) and the European Medicines Agency. Stem cell transplant is also used to treat CMML, and involves the transplantation of donor haematopoietic stem cells into the recipient. Blood transfusion and erythropoietin are used to treat disease associated anaemia.

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope.

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.

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.

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.

Hepatosplenic T-cell lymphoma is a rare and generally incurable form of lymphoma.

Hepatosplenic T-cell lymphoma is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liver, spleen, and bone marrow.

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

Richter's syndrome (RS), also known as Richter's transformation, is a transformation which occurs in about 5-10% of B cell chronic lymphocytic leukemia (CLL) and hairy cell leukemia into a fast-growing diffuse large B cell lymphoma, a variety of non-Hodgkin lymphoma which is refractory to treatment and carries a bad prognosis. There is also a less common variant in which the CLL changes into a Hodgkin's lymphoma. Rarely, transformations to a form of myeloid leukemia have been observed. These extraordinarily rare transformations carry a very poor prognosis.

Richter's transformation affects about 5% of CLL patients at some point during their lives.

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.

EATL can be classified as an extranodal peripheral T cell lymphoma, a category it shares with hepatosplenic T cell lymphoma and panniculitic T cell lymphoma.

It can be further classified in type I and II EATL.

Plasma cell granuloma is a lesional pattern of inflammatory pseudotumour, different from the "inflammatory myofibroblastic tumor" pattern.

It is linked to IgG4-related disease.

Hematopoietic stem cells give rise to: 1) myeloid precursor cells that differentiate into red blood cells, mast cells, blood platelet-forming megakaryocytes, or myeloblasts, which latter cells subsequently differentiate into white blood cells viz., neutrophils, basophils, monocytes, and eosinophils; or 2) lymphoid precursor cells which differentiate into T lymphocytes, B lymphocytes, or natural killer cells. Malignant transformation of these stem or precursor cells results in the development of various hematological malignancies. Some of these transformations involve chromosomal translocations or Interstitial deletions that create fusion genes. These fusion genes encode fusion proteins that continuously stimulate cell growth, proliferation, prolonged survival, and/or differentiation. Such mutations occur in hematological stem cells and/or their daughter myeloid precursor and lymphoid precursor cells; commonly involve genes that encode tyrosine kinase proteins; and cause or contribute to the development of hematological malignancies. A classic example of such a disease is chronic myelogenous leukemia, a neoplasm commonly caused by a mutation that creates the "BCR-ABL1" fusion gene (see Philadelphia chromosome). The disease is due to conversion of the tightly regulated tyrosine kinase of ABL1 protein to being unregulated and continuously active in the BCR-ABL1 fusion protein. This Philadelphia chromosome positive form of chronic myelogenous leukemia used to be treated with chemotherapy but nonetheless was regarded as becoming lethal within 18-60 months of diagnosis. With the discovery of the uncontrolled tyrosine kinase activity of this disorder and the use of tyrosine kinase inhibitors. Philadelphia chromosome positive chronic myelogenous eukemia is now successfully treated with maintenance tyrosine kinase inhibiting drugs to achieve its long-term suppression.

Some hematological malignancies exhibit increased numbers of circulating blood eosinophils, increased numbers of bone marrow eosinophils, and/or eosinophil infiltrations into otherwise normal tissues. These malignancies were at first diagnosed as eosinophilia, hypereosinophilia, acute eosinophilic leukemia, chronic eosinophilic leukemia, other myeloid leukemias, myeloproliferative neoplasm, myeloid sarcoma, lymphoid leukemia, or non-Hodgkin lymphomas. Based on their association with eosinophils, unique genetic mutations, and known or potential sensitivity to tyrosine kinase inhibitors or other specific drug therapies, they are now in the process of being classified together under the term clonal hypereosinophilia or clonal eosinophilia. Historically, patients suffering the cited eosinophil-related syndromes were evaluated for causes of their eosinophilia such as those due to allergic disease, parasite or fungal infection, autoimmune disorders, and various well-known hematological malignancies (e.g. Chronic myelogenous leukemia, systemic mastocytosis, etc.) (see causes of eosinophilia). Absent these causes, patients were diagnosed in the World Health Organization's classification as having either 1) Chronic eosinophilic leukemia, not otherwise specified, (CEL-NOS) if blood or bone marrow blast cells exceeded 2% or 5% of total nucleated cells, respectively, and other criteria were met or 2) idiopathic hypereosinophilic syndrome (HES) if there was evidence of eosinophil-induced tissue damage but no criteria indicating chronic eosinophilic leukemia. Discovery of genetic mutations underlining these eosinophilia syndromes lead to their removal from CEL-NOS or HES categories and classification as myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Informally, these diseases are also termed clonal hypereosinophilias. New genetic mutations associated with, and possibly contributing to the development of, eosinophilia have been discovered, deemed to be causes of clonal eosinophilia, and, in certain cases, recommended for inclusion in the category of myeloid and lymphoid neoplasms associated with eosinophilia and abnormalities of "PDGFRA, PDGFRB, FGFR1," and, tentatively, "PCMA-JAK2". Many of the genetic causes for clonal eosinophilia are rare but nonetheless merit attention because of their known or potential sensitivity to therapeutic interventions that differ dramatically form the often toxic chemotherapy used to treat more common hematological malignancies.

Swelling of the lymph nodes in the neck is the initial presentation in many people, and the diagnosis of NPC is often made by lymph node biopsy. Signs and symptoms related to the primary tumor include trismus, pain, otitis media, nasal regurgitation due to paresis (loss of or impaired movement) of the soft palate, hearing loss and cranial nerve palsy (paralysis). Larger growths may produce nasal obstruction or bleeding and a "nasal twang". Metastatic spread may result in bone pain or organ dysfunction. Rarely, a paraneoplastic syndrome of osteoarthropathy (diseases of joints and bones) may occur with widespread disease.

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.