Combined estrogen and progestin hormone therapy (CHT) increases breast cancer risk, but this risk varies by breast cancer type. Several studies indicate that CHT is more strongly related to lobular carcinoma risk than to ductal carcinoma risk, but these studies have been limited in their assessments of recency and duration of use, and none included a centralized pathology review. We conducted a population-based case-control study consisting of 324 lobular, 196 ductal-lobular, and 524 ductal cases diagnosed from 2000 to 2004 and 469 controls ages 55 to 74 years old. Tissue specimens were centrally reviewed for 83% of cases. Associations between hormone use and breast cancer risk were evaluated using polytomous logistic regression. Current CHT users had 2.7-fold [95% confidence interval (95% CI), 1.7-4.2] and 3.3-fold (95% CI, 2.0-5.7) elevated risks of lobular and ductal-lobular carcinomas, respectively, regardless of tumor stage, size, or nodal status. Elevations in risk were observed only among users of CHT for > or =3 years. Among ductal-lobular cases, CHT increased risk of tumors that were > or =50% lobular (odds ratio, 4.8; 95% CI, 2.1-11.1) but not tumors that were <50% lobular (odds ratio, 1.9; 95% CI, 0.9-4.1). Current CHT users for > or =3 years have a substantially increased risk of lobular carcinomas. Although lobular carcinomas are less common than ductal carcinomas ( approximately 16% versus 70% of all invasive breast cancers in the United States), this duration is shorter than the 5 years of use widely cited to be needed to confer an increased risk of breast cancer overall. Further studies focusing on the etiology of lobular carcinomas are needed.