One hundred twenty-seven white European patients with differentiated thyroid cancer were typed for human lymphocyte antigen (HLA) DR specificities. There was no significant deviation from the HLA-DR distribution observed in 160 normal patient controls, neither in the entire group nor in the patient groups with nonmedullary types of thyroid cancer (61 with papillary and 44 with follicular, all nonradiation associated). Also, subdivision of patients with nonmedullary thyroid cancer according to age at diagnosis, presence of metastases, and presence of thyroglobulin antibodies in serum showed no significant deviation from the HLA-DR distribution. For the patients with medullary thyroid cancer (only sporadic [n = 20] or inherited isolated [n = 2] forms, no multiple endocrine neoplasias), there was a significant increase of HLA-DR2 (11 of 22 cases [50%]) in comparison with control patients (22%; P corrected to 0.02; relative risk, 3.6). These data suggest, in contrast to previous reports, that there is no genetic influence on the development of nonmedullary types of differentiated thyroid cancer. Medullary thyroid cancer without multiple endocrine neoplasia, however, may be associated with HLA-DR2.