Ameloblastoma is an odontogenic tumor with a variety of histologic appearances and an unpredictable biologic behavior. Little is known about allelic losses of tumor suppressor genes in ameloblastomas. This study surveyed DNA damage in ameloblastomas and correlated this with histologic sub-type and clinical outcome. There were 12 ameloblastomas (two peripheral, eight solid, and two unicystic) and three ameloblastic carcinoma studied for loss of heterozygosity of tumor suppressor genes on chromosomes 1p, 3p, 9p,10q, and 17p (L-myc, hOGG1, p16, pten, and p53). The frequency of allelic loss and the intratumoral heterogeneity were calculated. L-myc (71% frequency of allelic loss) and pten (62% frequency of allelic loss) had the most frequent allelic losses. Overall frequency of allelic loss and intratumoral heterogeneity were higher in mandibular and in unicystic tumors and lower in tumors that recurred/metastasized. The rate of allelic loss in the three carcinomas was similar to that seen in benign tumors. The frequency of allelic loss and intratumoral heterogeneity did not correlate with age, gender, histologic subtype, or prognosis. Since tumors that behaved aggressively did not harbor more allelic losses, it is likely that DNA damage in ameloblastomas and ameloblastic carcinomas is sporadic and cumulative. We conclude that other genetic or epigenetic mechanisms may be responsible for malignant behavior in ameloblastic carcinomas.