We reviewed 72 cerebrospinal fluid (CSF) specimens with abnormal hematopoietic cells and the clinical records of the 45 patients from whom they were obtained. Of the 72 specimens, 34 were originally diagnosed as positive for lymphoma or leukemia and the remaining 38 as "atypical cells present." Based on follow-up information of the patients, only three "atypical" specimens were from patients with CSF leukemia, but ten of the positive diagnoses were incorrect. Cases of acute lymphoblastic leukemia (ALL) produced cells with a characteristic morphology. Cells of five of the six false-positive specimens in this disorder were, in retrospect, markedly different from typical blasts. In contrast, two false-positive reactive cases from patients with no established malignancy had an infiltrate whose morphology was indistinguishable from that of many cases of diffuse histiocytic lymphoma (DHL). There were no cases of chronic lymphocytic leukemia (CLL) or nodular poorly differentiated lymphocytic lymphoma involving CSF, but two patients with CLL and infectious meningitis had false-positive cytologies. We conclude that in evaluating CSF specimens for lymphoma or leukemia, knowledge of the morphology and behavior of a patient's particular tumor can minimize incorrect diagnostic interpretations.