Background: With an increasing elderly population, the United States will experience an increased cancer burden in the coming years. We evaluated associations between anthropometric, lifestyle, and reproductive factors and risk of breast, ovarian, and colorectal cancer in a prospective study of postmenopausal women with a focus on diagnoses occurring among very elderly women (75 years). Methods: For each cancer type, we estimated associations with relevant exposures in 2 age bands (<75 vs. 75 years of age). During 22 years of follow-up, 322 ovarian, 1,311 colon, 315 rectal, and 2,664 breast cancers occurred among 37,459 postmenopausal women (mean age at baseline 62 years, range 55-71 years). Results: For ovarian cancer, we identified few significant associations in either age band. Colon cancer cases had a higher body mass index and were less likely to report estrogen or aspirin use than non-cases, yet these associations were consistent in both age bands. Few risk factors were identified for rectal cancer in women of 75 years of age or more. For breast cancer, notably different patterns were revealed, with alcohol consumption associated with risk in the younger group and previous hysterectomy associated with risk only in the older group. Conclusion: These analyses suggest some important differences in risk factors for cancer depending on the age at diagnosis. Impact: This study suggests that etiologic differences may exist in cancers occurring in the very elderly women. The ongoing demographic shift in the United States provides a strong rationale for studies evaluating cancer etiology in the elderly.