Scanning DNA-cytophotometry was performed on touch imprints of 26 lymph nodes (LN) obtained from 25 patients with cutaneous T-cell lymphoma (CTCL), stained by the Feulgen technique, and interpreted without knowledge of histopathologic diagnosis. Four patterns of DNA distribution were identified, but only histograms that demonstrated cells containing nuclei with more than 4C DNA content (hypertetraploidy) reliably distinguished LN involved with CTCL from LN with reactive changes; for example, dermatopathic lymphadenitis. An abnormal DNA histogram with evidence of hypertetraploidy was demonstrated in 9 of 12 LN showing histopathologic evidence of involvement compared with no abnormal histograms in 14 LN without histopathologic involvement. One LN that was diffusely involved with CTCL had a DNA distribution characteristic of a relatively high level of cell proliferation, but without definite hypertetraploidy. Cytogenetic studies on the blood of this patient, who had Sézary syndrome, demonstrated a clone of lymphocytes with a pseudodiploid karyotype without a related polyploid subline. The remaining two histopathologically involved LN had normal DNA histograms; these LN were only focally involved with CTCL. These observations indicate that DNA-cytophotometry correlates well with the histopathologic findings in LN diffusely involved with CTCL, but may be normal in LN with focal involvement or in those that contain cytogenetically abnormal cells with a near-diploid DNA content.