Gallium (67Ga) scan was performed in 29 CLL patients with chronic lymphocytic leukemia who were suspected on clinical grounds to have Richter's transformation (RT). Of 29 patients, nine had a positive 67Ga scan; seven of these had a subsequent biopsy that verified large-cell lymphoma or Hodgkin's disease. The other two patients underwent biopsies that revealed fungal infections, a known cause of 67Ga uptake. Two patients had biopsies that were consistent with RT but showed no affinity to 67Ga. One false negative resulted five days after chemotherapy, a known cause of diminished 67Ga uptake. The other occurred within a small infraorbital mass, containing only 10% centroblasts, which is below the level of detection for 67Ga scanning. Subsequent 67Ga scans in both patients revealed 67Ga avid lesions, which demonstrated RT upon biopsy. This technique was more strongly predictive of RT than was measurement of serum B-2 microglobulin or serum lactate dehydrogenase levels. 67Ga scanning is very useful in localizing an optimal site for biopsy to document RT; it may also have the potential to help assess response to treatment, predict recurrence, and contribute to long-term follow-up in this subset of patients.