To assess sclerosing adenosis (SA) as an independent risk factor for subsequent invasive breast cancer (IBC), the authors reviewed 10,366 benign breast biopsy specimens (BB) obtained between 1950 and 1968 and identified 547 cases of SA meeting strict histologic criteria of expanded lobular units with whorled compressed acini. Of those women targeted for follow-up (3303, of whom 349 had SA), 84% were successfully followed for an average of 17 years. The relative risk for IBC among patients with SA regardless of the presence of atypical hyperplasia (AH) was 2.1. This risk decreased to 1.7 when patients with AH were excluded, and rose to 6.7 when only those patients with SA and AH were analyzed. The coexistence of a family history of IBC in a first-degree relative did not further elevate risk above that of SA alone when women with AH were excluded. Sclerosing adenosis was found to be positively associated with atypical lobular hyperplasia (ALH) as ALH was present in biopsy specimens with SA 2.7 times more frequently than in other biopsy specimens. Perimenopausal age, histologic calcification, and family history of IBC (FH) were also positively associated with SA. Sclerosing adenosis was most frequent in the perimenopausal period and had a weak association with family history of IBC. No association with atypical ductal hyperplasia (ADH) was identified. The authors conclude sclerosing adenosis represents an independent risk factor for subsequent invasive breast cancer apart from its association with ALH, and the risk (excluding patients with coexistent atypical hyperplasia) is in the range of 1.7, times thereby justifying inclusion of sclerosing adenosis as a component of a group of histopathologically defined lesions termed "proliferative breast disease without atypia" which implies a relative cancer risk of 1.5 to 2.0.