BACKGROUND: A point mutation in the RET proto-oncogene, in medullary thyroid carcinoma (MTC) is well known, but no other genetic causes of MTC have been found. This study was performed to identify the most common DNA copy number changes in MTC by comparative genomic hybridization (CGH). METHODS: Twenty-nine surgically resected MTC specimens were retrospectively selected from patients operated on between 1996 and 2004 at the Asan Medical Center. A review of the clinical data and pathological findings was performed. Congored staining and immunohistochemical stains (calcitonin, chromogranin A and CEA) were processed by tissue microarray. CGH analysis was performed. RESULTS: The Congo-red stain was positive in only 12 cases. The immunohistochemical results were positive in 29 cases for chromogranin A, 26 cases for CEA and 25 cases for calcitonin. DNA copy number changes were found in 23 cases (79.3%). The most frequent change was a gain of 19q (65.5%); less frequent changes were gain of 22 (55.2%), 19p (51.7%), 16p (27.58%), 17q (17.24%), and loss of 4q (27.6%) and 3p (17.24%). CONCLUSIONS: DNA copy number changes of MTC were more common (79.3%) than reported in previous studies. The most frequent changes were gains in 19q, 22 and 19p.