We often meet patients and colleagues who ask what tests are needed to determine the diagnosis, comprehensively assess the disease and judge the prognosis when they encounter swollen lymph nodes or suspect lymphoma? Generally speaking, the diagnosis of lymphoma is rather complicated, and if you want to comprehensively assess the disease, more items need to be examined, and the specific items and meanings are as follows: 1. Routine blood tests Most of the blood images are normal in patients at the early stage of initial diagnosis, but when the disease progresses, bone marrow involvement, hypersplenism, and after multiple chemotherapy and radiotherapy, there can be a decrease in the three lines. In patients with NHL with bone marrow involvement, especially those with high malignancy, lymphoma cells can be found in peripheral blood smears in nearly half of the patients. The rate of bone marrow invasion at the time of lymphoma diagnosis can be as high as 30%, with different histological subtypes and different clinical stages. Approximately 70% of lymphoma bone marrow invasion is focal, while 30% is diffuse and interstitial. Therefore, multisite aspiration and biopsy are expected to increase the rate of positive tests. Invaded bone marrow cells are characterized by nuclear distortion and marked nuclear division. Immunophenotypic analysis can further clarify the origin of the cells. 3.Serological examination Lactate dehydrogenase (LDH) and β2-microglobulin levels represent the metabolic level of tumor cells and tumor load, and the detection of these indicators is a predictor of disease recurrence and tumor residual. Soluble interleukin-2 receptor (IL-2R) as well as tumor necrosis factor (TNF) can also be used as serological tumor load parameters. 4.Imaging X-ray has an important reference value for the diagnosis of malignant lymphoma. At present, routine X-ray examinations include posterior anterior and lateral chest films, supplemented with body layer photography if necessary, in order to observe the lymph nodes under the hilum, mediastinum and tracheal bulge, and also to observe whether there is any invasion in the lung. CT, magnetic resonance, and color ultrasound examinations are very helpful to detect lesions in the mediastinum, retroperitoneum and other hidden areas. In addition, the dynamics and proliferation degree of tumor cells can be directly detected by isotope scan such as H3 labeling. 5.Histopathological examination Pathological examination of lymph nodes or other involved tissues is the main basis for confirming the diagnosis of NHL and the type of pathology, and malignant lymphoma usually needs to be confirmed by pathological examination. Light microscopic examination of lymph nodes not only needs to observe the morphology of cells, but also the structure and interstitial cell reaction of the whole lymph nodes, so it is better to take complete lymph nodes for examination and not partial lymph nodes if possible. Although needle aspiration biopsy has some reference value for diagnosis, it often does not provide enough material to make a comprehensive diagnosis, and needle aspiration is also prone to hematoma. In the following cases, the possibility of malignant lymphoma should be taken seriously, and it is best to take lymph nodes for pathological examination in a timely manner, with the best site being the neck: (1) Progressive lymph node enlargement without a clear cause, especially when the site, hardness, and activity are consistent with the aforementioned characteristics of malignant lymphoma; (2) Lymph node tuberculosis after regular anti-tuberculosis or chronic lymph node inflammation after general anti-inflammatory treatment has failed; (3) Lymph node enlargement and (3) Recurrent fever with a general tendency to be progressive; (4) Unexplained prolonged low-grade fever or periodic fever, especially with pruritus, excessive sweating, and wasting, and superficial lymph node enlargement, especially bilateral lymph node enlargement in the talus. (5) Immunohistochemical examination Immunohistochemical examination can determine the origin and degree of differentiation of lymphoma cells. Currently, effective and stable paraffin section labeling antibodies commonly used are L26 (all B, except plasmacytoma only), CD45R, CD3, UCHL-1 (all T); T lymphoma application of CD4 and CD8 labeling can distinguish between helper T cells and suppressor T cells; KP1, MAC387, lysozyme and α1 antitrypsin can be tissue cell markers; increased expression of KI-67 represents early relapse and shortened survival. (6) Cytogenetic and molecular biological examinations Molecular genetic analysis of NHL shows that more than 90% of cases have chromosomal abnormalities, and these chromosomal aberrations are non-random. The most common chromosomal aberrations are reciprocal translocations at one stage, for example, t(8;14)(q24;q32), t(8;22)(q24;q11) or t(2;8)(p11;q24) are seen in 90% of highly malignant Burkitt’s lymphomas, while t(14;8)(q32;q21) is seen in 80-85% of follicular lymphomas. These chromosomal fragments often affect immunoglobulin genes and oncogenes as a result of reciprocal translocations. For example, Burkitt’s lymphoma has the oncogene C-MYC near the chromosome 8 breakpoint, and overexpression of the translocated oncogene protein leads to abnormal cell proliferation. In fact, the above tests are not necessary for every patient with lymphoma and swollen lymph nodes. The specific situation needs to be considered by the hematologist according to the patient’s condition, financial situation and the level of treatment in the hospital.