The roles of carotenoids, retinol, and tocopherols in breast cancer etiology have been inconclusive. The authors prospectively assessed the relations between plasma α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, α-tocopherol, and γ-tocopherol and breast cancer risk by conducting a nested case-control study using plasma collected from women enrolled in the Nurses’ Health Study. A total of 969 cases of breast cancer diagnosed after blood draw and prior to June 1, 1998, were individually matched to controls. The multivariate risk of breast cancer was 25–35% less for women with the highest quintile compared with that for women with the lowest quintile of α-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47, 0.88; ptrend = 0.01), β-carotene (OR = 0.73, 95% CI: 0.53, 1.02; ptrend = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55, 1.01; ptrend = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55, 1.05; ptrend = 0.05). The inverse association observed with α-carotene and breast cancer was greater for invasive cancers with nodal metastasis. The authors conclude that some carotenoids are inversely associated with breast cancer. Although the association was strongest for α-carotene, the high degree of collinearity among plasma carotenoids limits our ability to conclude that this association is specific to any individual carotenoid.