The role of dipeptidyl aminopeptidase IV (DAP IV) activity staining in the investigation of a thyroid mass was explored. The study consisted of two parts: the first part involved DAP IV staining performed on various thyroid lesions sampled from operative specimens. These included frozen tissues or cytologic smears. The second part of the study, which is ongoing, prospectively examines the DAP IV activity in fine-needle aspiration (FNA) specimens from patients with a thyroid mass. Results from part 1 of the study indicated that DAP IV activity staining was a useful adjunct in distinguishing differentiated carcinoma from benign lesions, particularly the "follicular lesions." Preliminary findings of the second part of the study suggest that DAP IV staining can be applied to FNA specimens. The measure of DAP IV activity and its influence on the diagnostic accuracy of FNA remain to be seen.