Objective: Flow cytometry is proving useful in the evaluation of lymphoproliferative disorders. In a case series, the authors investigated the safety of cross-sectional fine-needle aspiration biopsy of the spleen under sonographic guidance, and the usefulness of flow cytometry in analysis of biopsy samples., Methods: Five patients underwent fine-needle biopsy with freehand sonographic guidance. Samples were analyzed on a flow cytometer., Results: Through cytologic examination enhanced by flow cytometry, 2 cases of lymphoma, 1 case of metastatic transitional cell carcinoma, and 1 case of focal splenic hemangioma were diagnosed. Normal lymphocytes were demonstrated in 1 case, in which long-term follow-up of splenomegaly showed that this was related to cirrhosis and portal hypertension in a patient with a history of treated non-Hodgkin's lymphoma., Conclusion: Flow-cytometry-enhanced fine-needle aspiration of the spleen is a safe and useful tool for the interventional radiologist. In our institution, it evolved as the result of effective teamwork between diagnostic radiologists and pathologists. Flow cytometry promises to be increasingly useful in the diagnosis and management of lymphoproliferative diseases.