Gray zone lymphoma is more difficult to treat. Gray zone lymphoma is a specific type of lymphoma, i.e., it has pathologic staging and immunologic features that are intermediate between two types of lymphoma and cannot be classified as either type of lymphoma. Examples include B-cell lymphomas between diffuse large B-cell lymphoma (DLBCL) and Burkitt’s lymphoma (BL) that cannot be clearly classified. Gray zone lymphomas are by nature malignant diseases of the blood system, and most are highly aggressive lymphomas that are difficult to cure completely. Treatment may include combination chemotherapy (CDOP regimen) as the first-line treatment for non-Hodgkin’s lymphoma, molecularly targeted therapy (e.g., rituximab, etc.) or hematopoietic stem cell transplantation. Gray zone lymphoma is difficult to treat and has a high degree of individual variability in outcome. It is recommended that the patient should consult a hematologist in a timely manner to have the patient’s condition evaluated by a specialist and to develop an individualized treatment plan.