Subacute thyroiditis (SAT) is a spontaneously remitting inflammatory disorder of the thyroid, associated with human leukocyte antigen (HLA)-B35, and may be virally induced in genetically predisposed individuals. A 57-year-old Caucasian man presented with symptoms of hyperthyroidism as well as enlargement and tenderness of the thyroid. The patient had an elevated erythrocyte sedimentation rate, low thyrotropin (TSH) and elevated thyroxine and triiodothyroinine levels with suppressed 131I thyroidal uptake. He was diagnosed to have SAT. In the patient's family three sisters and one brother also had had SAT, as probably did the deceased father. Because of the familial occurrence HLA-typing was performed. All affected family members were heterozygous for HLA-B35. The family members lived more than 50 miles apart in different regions of The Netherlands and had SAT at different time points between 1986 and 2002, which in combination with HLA-B35 seems to highlight the importance of genetic influences as a risk factor for the development of SAT in this family. In conclusion, the case described here represents the second familial incidence and largest family reported so far with occurrence of SAT in association with HLA-B35.