Lymphoma: This is often the first consideration due to the common presentation of lymphoma with both splenomegaly and lymphadenopathy. Lymphomas, such as Hodgkin lymphoma and non-Hodgkin lymphoma, can cause enlargement of the spleen and lymph nodes.

Chronic Lymphocytic Leukemia (CLL): CLL can present with splenomegaly and lymphadenopathy due to the accumulation of malignant lymphocytes in these organs.
Chronic Myeloid Leukemia (CML): Although more commonly associated with splenomegaly, CML can also cause lymphadenopathy, especially in advanced stages.
Infectious Mononucleosis: Caused by Epstein-Barr virus (EBV), this condition can lead to both splenomegaly and lymphadenopathy, particularly in the cervical region.
Tuberculosis: Although less common in some regions, tuberculosis can cause splenomegaly and lymphadenopathy, especially in the context of disseminated disease.

Histiocytosis: Including Langerhans cell histiocytosis and other rare forms, these conditions can present with splenomegaly and lymphadenopathy and have significant implications for treatment and prognosis.
Sarcoidosis: While often presenting with pulmonary symptoms, sarcoidosis can also cause splenomegaly and lymphadenopathy, and missing this diagnosis could lead to inappropriate treatment.
Malignant Histiocytosis: A rare but aggressive condition that can mimic lymphoma and requires prompt diagnosis and treatment.

Gaucher's Disease: A genetic disorder that can lead to splenomegaly due to the accumulation of glucocerebroside, and occasionally lymphadenopathy.
Niemann-Pick Disease: Another genetic disorder that can cause splenomegaly and, less commonly, lymphadenopathy due to lipid accumulation.
Castleman Disease: A rare disorder that can present with lymphadenopathy and occasionally splenomegaly, often mimicking lymphoma.
Systemic Mastocytosis: A condition characterized by the accumulation of mast cells in various organs, including the spleen and lymph nodes, leading to their enlargement.