We studied the role of fine-needle aspiration (FNA) in the evaluation of lymphadenopathy associated with cutaneous T-cell lymphoma (CTCL) in 11 patients with lymphadenopathy and compared findings with corresponding histologic material. Molecular genetic analysis for T-cell clonality by polymerase chain reaction (PCR) was performed on all aspirates. Immunophenotyping was successful in 4 of 7 cases in which flow cytometry was attempted from the aspirated material. Cytologic evaluation of FNA samples correlated strongly with histologic rating of involvement based on numbers of atypical cerebriform lymphocytes in the nodal specimen. Of 7 nodal specimens with scattered or small groups of atypical cells in the background of dermatopathic lymphadenopathy (LN1-2), the cytologic diagnosis was interpreted as reactive in all instances. Of 4 specimens with highly suspect (LN3) or definite histologic involvement (LN4), the cytologic diagnosis was likewise suspect or malignant. The correlation between molecular genetic studies on FNA samples and studies on tissue was not significant; in 2 cases, a T-cell clone was detected in the nodal tissue sample but not in the FNA sample, suggesting undersampling. A T-cell clone was detected by PCR in 5 of 7 nodal specimens judged reactive by FNA biopsy or histologic assessment. FNA for cytologic and molecular genetic analysis is a useful method to evaluate lymphadenopathy associated with CTCL and may obviate the need for surgical biopsy.