This study addresses the utility of fine-needle aspiration (FNA) in assessing lymphadenopathy in patients with and without a previous history of malignancy. We reviewed the FNAs of superficial and deeply seated lymph nodes performed at our institution over a period of 18 yr (1983-2001). Where applicable, we also reviewed and report here the results of subsequent surgical excisional biopsies. We analyzed data from 439 patients, who ranged in age from 1 to 90 yr. The neck and retroperitoneum were the most frequently sampled sites (47% and 25%, respectively). Among the 439 FNAs, adequate material was obtained in 421 cases (96%); the remaining 18 were unsatisfactory (4.1%). Malignant diagnoses were rendered in 330 cases (75% of 439), four were suspicious for lymphoma (0.9%), and 87 were read as reactive lymph nodes or granulomas (20%). The most common malignant cytologic diagnoses from these lymph node FNAs were adenocarcinoma, squamous cell carcinoma, and lymphoma. We compared results between two major groups: patients with a history of malignancy and those without. FNA showed malignancy in 87% of patients with a history of cancer and 41% without such a history. Thirty-three or 10% of patients with a history of malignancy were given a benign diagnosis and follow-up surgical excisional biopsies were performed in nine of these cases. Four of the nine showed low-grade lymphoma. Of the 18 non-diagnostic FNAs, nine came from patients with a history of malignancy and in six of these nine who had a follow-up surgical excisional biopsy the lymph nodes were positive for malignancy. Of the other nine, who had no history of malignancy, only two had follow-up biopsies and both of these were negative. Patients with a history of malignancy are more than twice as likely to show malignancy on lymph node FNA compared to those without such a history (87% vs. 41%). Knowing whether a patient has a history of malignancy provides the appropriate level of suspicion for ordering ancillary investigations or even recommending excisional biopsy for further evaluation.