The prohibitin gene, mapped to chromosome 17q21 is a candidate tumor suppressor gene. Because several somatic mutations of prohibitin were detected in breast tumors, we sought to identify potential carriers of prohibitin gene mutations in selected patients with early onset breast cancer. Seventy-six patients who developed breast cancer at or before the age of 40 were examined for mutations of prohibitin within the most conserved regions of the gene. Additionally, all exons of the prohibitin gene were examined in a subgroup of patients with a history of first-degree relatives with primary breast cancer. While several polymorphisms were noted, no inherited mutations of prohibitin were identified. This study suggests that prohibitin is not an early onset breast cancer susceptibility gene and additional studies will be necessary to understand its role in sporadic breast cancer progression.